BACKGROUND The aim of this study was to assess the ability of polyethylenimine (PEI) as an E1A plasmid vector to transfect hepatocellular carcinoma SMMC-7721 cells and to analyze the sensitization effect of E1A on various anti-tumor drugs. MATERIAL AND METHODS PEI-mediated recombinant plasmid psv-E1A with high expression of the E1A gene was introduced into hepatocellular carcinoma SMMC-7721 cells, and the effective transfection of E1A gene was determined by RT-PCR and Western blot analysis. The CCK8 method was used to detect the proliferation inhibition of docetaxel, epirubicin, gemcitabine, and 5-fluorouracil on SMMC-7721 cells before and after the transfection of the E1A gene. RESULTS RT-PCR and Western blot analysis showed that PEI could transfect plasmid psv-E1A with stable expression. After the transfection of E1A gene, the sensitivity of SMMC-7721 cells to docetaxel, epirubicin, gemcitabine, and 5-fluorouracil was increased (P<0.05), and the sensitivity to docetaxel was significantly improved (P<0.01). CONCLUSIONS PEI can transfect plasmid psv-E1A. The E1A gene can increase the sensitivity of hepatocellular carcinoma cells to chemotherapeutic drugs. The mechanism may be related to the increased ability of the E1A gene to inhibit proliferation of hepatocellular carcinoma cells and altering the cell cycle of hepatocellular carcinoma cells.