Objective To evaluate the therapeutic efficacy and toxicity of oxaliplatin (OXA) -based systemic chemotherapy in patients with advanced hepatocellular carcinoma (HCC) . Methods Thirty patients with advanced HCC admitted to our hospital from June 2009 to June 2013 were randomly divided into Cape OX group (15 patients, treated with OXA and capecitabine or CAP) and FOLFOX group (15 patients, treated with OXA and calcium folinate or CF, followed by fluorouracil or 5-FU) . The therapeutic effects were evaluated after two cycles of treatment using the Response Evaluation Criteria in Solid Tumors (RECIST 1. 1) . Assessment criteria included overall response rate (OR) , time to tumor progression (TTP) , and overall survival (OS) analyzed by Kaplan-Meier survival curves, as well as the toxicity profile of the combination chemotherapy. Comparison of OR was made by chi-square test; assessment of tumor response and toxicity profile was performed by Mann-Whitney U test; OS and TTP were analyzed by log-rank test. Results In the Cape OX group, the OR was13. 3%, and the mean OS and TTP were 10. 4 months and 5. 0 months, respectively. In the FOLFOX group, the OR was 6. 7%, and the mean OS and TTP were 9. 0 months and 4. 7 months, respectively. The differences between the two groups had no statistical significance in all three parameters (P = 0. 543, 0. 606, and 0. 769, respectively) . Compared with the FOLFOX group, the Cape OX group had significantly lower toxicity rates in gastrointestinal tract and myelosuppression (P = 0. 006 and 0. 002, respectively) . Conclusions The OXA-based systemic chemotherapy shows anti-tumor effects for advanced HCC, and there is no significant difference in efficacy between the two regimens. Decisions regarding the choice of specific treatment should be based on the patients' clinical conditions.