OBJECTIVE:To investigate the efficacy of an herbal formula of Bushen Jianpi(补肾健脾方,BSJP)com-bined with sorafenib on hepatocellular carcinoma(HCC)in vitro and in vivo,and to study the underly-ing mechanisms of action.METHODS:BSJP,a mixture of 12 raw herbs,was ex-tracted in 70％alcohol/30％water and freeze-dried into a powder.The in vitro effects of BSJP alone,sorafenib alone,and their combination on cell sur-vival,apoptosis,and cell cycle distribution were evaluated in HCC cell lines HCCLM3,HepG2,and SMMC-7721.The expression of B-cell lymphoma-2(Bcl-2),caspase-3,and caspase-9 in HCCLM3 cells was measured using Western blots after drug ad-ministration.The in vivo effects of BSJP and sorafenib were evaluated in a tumor surgical resec-tion model using 4-week old male athymic BALB/c nude mice injected with HCCLM3 cells.Immunohis-tochemical analysis of tumor tissues was per-formed to evaluate the effects of BSJP alone,sorafenib alone,and their combination on the ex-pression of caspase-3,caspase-9,and Bcl-2.RESULTS:BSJP decreased the survival rate of HCC cell lines,and the combination of BSJP and sorafenib further decreased the survival rate.BSJP significantly promoted cell apoptosis and blocked cell-cycle progression in HCCLM3,HepG2,and SMMC-7721 cells in a dose-dependent manner.Fur-thermore,the administration of BSJP and sorafenib inhibited the growth of HCCLM3 cell xenografts in nude mice,with no reduction in body weight.In vi-vo and in vitro experiments showed that BSJP com-bined with sorafenib could significantly decrease the expression of Bcl-2.CONCLUSION:Our findings suggest that the herb-al formula of BSJP is a potential HCC antitumor agent.