Objective: To investigate the synergistic anti-tumor effect of QHF (a Chinese medicine formula with anti-tumor active ingredients, including 800 mg/kg Cinobufotalin, 14 mg/kg Ginsenoside Rg3, 5.5 mg/kg Notoginseng and 100 mg/kg Lentinan) when combined with the chemotherapy drug cisplatin (DDP). Methods: Hepatocellular carcinoma H22 cells were implanted into mice and after the transplants were successfully established the animals were divided into four groups, namely a normal saline(NS) control group, QHF group, DDP group and QHF+DDP group. The tumor growth was monitored and the survival time determined. In vitro studies employing H22 cells used the first three groups, and determined the effects of QHF and DDP on tumor cell cycle distribution, apoptosis and morphologic changes in vitro. Results: QHF significantly inhibited the growth of tumors and prolonged the survival time of mice with hepatocellular carcinomas. QHF combined with DDP could attenuate DDP-induced leucopenia, spleen and thymus atrophy and other indicators of toxicity. The inhibition rate of tumor growth reached 82.54% with QHF+DDP, and QHF prolonged the life span of DDP-treated mice by 66.83%. In the in vitro experiments tumor cells showed morphological changes characteristic of apoptosis by both light and transmission electron microscopy in the QHF group, and the apoptosis rate was 33.85%. Moreover, the proportion of cells in the G0/G1 phase was increased and those in the S-phase decreased. Conclusion: QHF combined with DDP could significantly inhibit tumor growth, induce the apoptosis of tumor cells and effectively attenuate DDP toxicity.