Three datasets were overlapped to mine CBX7-associated biological pathways. Both KEGG and GO analyses indicated that genes that were negatively correlated to CBX7 were strongly associated with the cell cycle pathway. Next, three GBM cell lines with different CBX7 abundance were chosen to further study the biological functions of CBX7. We observed that increased CBX7 protein levels inhibited glioma cells proliferation, migration and invasion. Then, we verified that CBX7 overexpression arrested cells in the G0/G1 phase. Moreover, we demonstrated that the underlying mechanism in CBX7 repression of CCNE1 promotor activity requiring HDAC2 recruitment and resulting in impaired CCNE1 transcription. Finally, orthotopic glioma models in nude mice implanted with CBX7-overexpressing U87 cells were used. Non-invasive bioluminescence imaging and survival times of nude mice revealed that CBX7 behaved as a tumor suppressor gene in gliomas.