Metformin has been shown to downregulate viral E6/E7 expression in HPV-positive cancer cells. However, Metformin does not induce cellular senescence, which is observed upon E6/E7 repression by RNA interference. Here we compare mass spectrometry-based proteome analyses of Metformin-treated SiHa cells (previously deposited to the ProteomeXchange Consortium with data set identifier PXC011095) with proteome analyses of SiHa cells transfected with si16E6/E7 or control siRNA (siCtrl-1) and grown for 72 hours to evaluate differences in the cell cycle regulation of HPV-positive cancer cells upon E6/E7 repression by Metformin or siE6/E7.