I started experiencing this issue today with QGIS 2.18.12 (Las Palmas) on WinServer 2008r2 in mid-session (for which I have no explanation, although Firefox also hung, whilst a number of other applications continued to run happily). Thereafter, QGIS start-up hung at 'setting up the GUI' The issue appears to be that the path to %OSGEO4W_ROOT%\apps\qgis\bin gets lost (which is where the GUI library qgis_gui.dll is stored). I managed to get QGIS to run by: 1. Run OSGeo4W Shell (as described above), either from start menu, or by running [QGIS-installation-folder]\OSGeo4W.bat 2. extend the PATH environment variable for the shell: path %OSGEO4W_ROOT%\apps\qgis\bin;%PATH% 3. Run QGIS (again as above): qgis 4. (and now for the weird bit) try running it from the normal shortcut - for me QGIS has started working again. Good luck!