BACKGROUND & OBJECTIVE: Chemotherapeutic protocols using adriamycin (ADM) is a standard treatment for hepatoblastoma, but the regime become less effective after the development of resistance to the drug.Recently, ADM in combination gene therapy has been used as an alternative treatment for hepatoblastoma.This study investigated the effect of ADM combined with human P21CIP1 transfection on the proliferation of hepatoblastoma cell line HepG2.METHODS: HepG2 cells were divided into empty control (no treatment), ADM group (treated with 0.5 μg/mL ADM), blank control group (transfected with blank plasmid pcDNA3), P21 group (transfected with plasmid pcDNA3-P21), and combination group (ADM treatment plus P21 transfection).The proliferation of HepG2 cells was determined by MTT assay.The mRNA level of p21 and survivin was detected by florescent quantitative polymerase chain reaction (FQ-PCR).RESULTS: After transfection, the mRNA level of p21 in P21 group was increased by 155 folds of as compared with that in empty control group (P<0.05).P21 inhibited the proliferation of HepG2 cells at Day 3 and Day 4 after the transfection (P<0.01).The rate of proliferation inhibition was significantly higher in combination group than in ADM group or P21 group (43.92% vs.32.97% and 35.77% at Day 3, P<0.01; 59.86% vs.39.35% and 40.96% at Day 4, P<0.01; 51.81% vs.33.91% and 10.68% at Day 5, P<0.01).This effect became stronger with time of co-treatment from Day 1 to Day 4 (r=0.91, P<0.05), and it was conspicuous at Day 4 (Q =1.07).The mRNA level of survivin was significantly lower in combination group than in P21 group and ADM group (P<0.01).CONCLUSION: P21 gene transfection plus ADM can effectively inhibit the proliferation of HepG2 cells and down-regulate the level of survivin mRNA, and promises to be a therapeutic alternative for human hepatoblastoma.