Abstract: Objective To explore the molecular mechanism of CTR9, a core component of PAF1c for RNA Polymerase II regulation,in regulating the proliferation, migration and invasion of hepatocellular carcinoma cells (HCCs). Methods The expression of CTR9 in hepatocellular carcinoma and adjacent non-tumor tissues was detected by Western bolt and immunohistochemistry. HepG2 and Huh7 cells were used for CTR9 silencing or transient transfection of exogenous CTR9. Then, EdU assay, colony formation assay, and Transwell assay were used to analyze the regulatory effects of CTR9 on the proliferation, migration and invasion of HCCs. Results CTR9 was highly expressed in hepatocellular carcinoma tissues. CTR9 silencing inhibited the proliferation, migration and invasion of HCCs, while overexpression of CTR9 promoted the proliferation, migration and invasion of HCCs. CTR9 positively regulated Akt/p-Akt. Conclusions CTR9 can promote the proliferation, migration and invasion of HCCs through positively regulating Akt/p-Akt.