diff --git a/pcsx2/gui/App.h b/pcsx2/gui/App.h
index 864b62cc92..2333c1a860 100644
--- a/pcsx2/gui/App.h
+++ b/pcsx2/gui/App.h
@@ -102,6 +102,7 @@ enum MenuIdentifiers
 	MenuId_RecentIsos_reservedStart,
 	MenuId_IsoBrowse = MenuId_RecentIsos_reservedStart + 100, // Open dialog, runs selected iso.
 	MenuId_IsoClear,
+	MenuId_IsoClearMissing,
 	MenuId_DriveSelector,
 	MenuId_DriveListRefresh,
 	MenuId_Ask_On_Booting,
diff --git a/pcsx2/gui/MainFrame.cpp b/pcsx2/gui/MainFrame.cpp
index 5a788aacf2..fea7390583 100644
--- a/pcsx2/gui/MainFrame.cpp
+++ b/pcsx2/gui/MainFrame.cpp
@@ -275,6 +275,7 @@ void MainEmuFrame::ConnectMenus()
 	// CDVD
 	Bind(wxEVT_MENU, &MainEmuFrame::Menu_IsoBrowse_Click, this, MenuId_IsoBrowse);
 	Bind(wxEVT_MENU, &MainEmuFrame::Menu_IsoClear_Click, this, MenuId_IsoClear);
+	Bind(wxEVT_MENU, &MainEmuFrame::Menu_IsoClearMissing_Click, this, MenuId_IsoClearMissing);
 	Bind(wxEVT_MENU, &MainEmuFrame::Menu_CdvdSource_Click, this, MenuId_Src_Iso);
 	Bind(wxEVT_MENU, &MainEmuFrame::Menu_CdvdSource_Click, this, MenuId_Src_Disc);
 	Bind(wxEVT_MENU, &MainEmuFrame::Menu_CdvdSource_Click, this, MenuId_Src_NoDisc);
diff --git a/pcsx2/gui/MainFrame.h b/pcsx2/gui/MainFrame.h
index 27e5dd0df3..f8fb480a95 100644
--- a/pcsx2/gui/MainFrame.h
+++ b/pcsx2/gui/MainFrame.h
@@ -162,6 +162,7 @@ protected:
 
 	void Menu_IsoBrowse_Click(wxCommandEvent& event);
 	void Menu_IsoClear_Click(wxCommandEvent& event);
+	void Menu_IsoClearMissing_Click(wxCommandEvent& event);
 	void Menu_EnableBackupStates_Click(wxCommandEvent& event);
 	void Menu_EnablePatches_Click(wxCommandEvent& event);
 	void Menu_EnableCheats_Click(wxCommandEvent& event);
diff --git a/pcsx2/gui/MainMenuClicks.cpp b/pcsx2/gui/MainMenuClicks.cpp
index 7d90ab2348..33a19f1656 100644
--- a/pcsx2/gui/MainMenuClicks.cpp
+++ b/pcsx2/gui/MainMenuClicks.cpp
@@ -579,6 +579,46 @@ void MainEmuFrame::Menu_IsoClear_Click(wxCommandEvent& event)
 	}
 }
 
+void MainEmuFrame::Menu_IsoClearMissing_Click(wxCommandEvent& event)
+{
+	auto& iso_manager = wxGetApp().GetRecentIsoManager();
+	const auto& missing_files = iso_manager.GetMissingFiles();
+
+	if (missing_files.empty())
+	{
+		wxDialogWithHelpers dialog(this, _("Information"));
+		dialog += dialog.Heading(_("No files to remove."));
+		pxIssueConfirmation(dialog, MsgButtons().OK());
+	}
+	else
+	{
+		wxDialogWithHelpers dialog(this, _("Confirm clearing ISO list"));
+		dialog += dialog.Heading(_("The following entries will be removed from the ISO list. Continue?"));
+
+		wxString missing_files_list;
+
+		for (const auto& file : missing_files)
+		{
+			missing_files_list += "* ";
+			missing_files_list += file.Filename;
+			missing_files_list += "\n";
+		}
+
+		dialog += dialog.Text(missing_files_list);
+
+		const bool confirmed = pxIssueConfirmation(dialog, MsgButtons().YesNo()) == wxID_YES;
+
+		if (confirmed)
+		{
+			// If the CDVD mode is not ISO, or the system isn't running, wipe the CurrentIso field in INI file
+			if (g_Conf->CdvdSource != CDVD_SourceType::Iso || !SysHasValidState())
+				SysUpdateIsoSrcFile("");
+			iso_manager.ClearMissing();
+			AppSaveSettings();
+		}
+	}
+}
+
 void MainEmuFrame::Menu_Ask_On_Boot_Click(wxCommandEvent& event)
 {
 	g_Conf->AskOnBoot = event.IsChecked();
diff --git a/pcsx2/gui/RecentIsoList.cpp b/pcsx2/gui/RecentIsoList.cpp
index 24670932a4..a17bdde600 100644
--- a/pcsx2/gui/RecentIsoList.cpp
+++ b/pcsx2/gui/RecentIsoList.cpp
@@ -38,6 +38,7 @@ RecentIsoManager::RecentIsoManager( wxMenu* menu, int firstIdForMenuItems_or_wxI
 	m_Separator	= nullptr;
 	m_ClearSeparator = nullptr;
 	m_Clear = nullptr;
+	m_ClearMissing = nullptr;
 
 	IniLoader loader;
 	LoadListFrom(loader);
@@ -116,6 +117,12 @@ void RecentIsoManager::RemoveAllFromMenu()
 		m_Menu->Destroy( m_Clear );
 		m_Clear = nullptr;
 	}
+
+	if (m_ClearMissing != nullptr)
+	{
+		m_Menu->Destroy(m_ClearMissing);
+		m_ClearMissing = nullptr;
+	}
 }
 
 void RecentIsoManager::Clear()
@@ -125,6 +132,40 @@ void RecentIsoManager::Clear()
 	Repopulate();
 }
 
+RecentIsoManager::VectorType RecentIsoManager::GetMissingFiles() const
+{
+	VectorType missing_files;
+
+	std::copy_if(
+		m_Items.begin(),
+		m_Items.end(),
+		std::back_inserter(missing_files),
+		[](const RecentItem& item) {
+			return !wxFileExists(item.Filename);
+		});
+
+	return missing_files;
+}
+
+void RecentIsoManager::ClearMissing()
+{
+	RemoveAllFromMenu();
+
+	VectorType existing_files;
+
+	std::copy_if(
+		m_Items.begin(),
+		m_Items.end(),
+		std::back_inserter(existing_files),
+		[](const RecentItem& item) {
+			return wxFileExists(item.Filename);
+		});
+
+	m_Items = existing_files;
+
+	Repopulate();
+}
+
 void RecentIsoManager::Repopulate()
 {
 	int cnt = m_Items.size();
@@ -138,6 +179,7 @@ void RecentIsoManager::Repopulate()
 		InsertIntoMenu( i );
 
 	m_ClearSeparator = m_Menu->AppendSeparator();
+	m_ClearMissing = m_Menu->Append(MenuIdentifiers::MenuId_IsoClearMissing, _("Clear missing files"));
 	m_Clear = m_Menu->Append(MenuIdentifiers::MenuId_IsoClear, _("Clear ISO list"));
 }
 
diff --git a/pcsx2/gui/RecentIsoList.h b/pcsx2/gui/RecentIsoList.h
index 480645f276..32e6897d5e 100644
--- a/pcsx2/gui/RecentIsoList.h
+++ b/pcsx2/gui/RecentIsoList.h
@@ -38,7 +38,11 @@ protected:
 		}
 	};
 
-	std::vector<RecentItem> m_Items;
+public:
+	using VectorType = std::vector<RecentItem>;
+
+protected:
+	VectorType m_Items;
 
 	wxMenu*		m_Menu;
 	uint		m_MaxLength;
@@ -49,15 +53,19 @@ protected:
 	wxMenuItem* m_Separator;
 	wxMenuItem* m_ClearSeparator;
 	wxMenuItem* m_Clear;
+	wxMenuItem* m_ClearMissing;
 
 public:
 	RecentIsoManager( wxMenu* menu , int firstIdForMenuItems_or_wxID_ANY );
 	virtual ~RecentIsoManager();
 
+	VectorType GetMissingFiles() const;
+
 	void RemoveAllFromMenu();
 	void EnableItems(bool display);
 	void Repopulate();
 	void Clear();
+	void ClearMissing();
 	void Add( const wxString& src );
 
 protected: