Background: To evaluate the therapeutic outcomes and the toxicity of the combination of arsenic trioxide and the Chinese traditional Jianpiliqi (JPLQ) formula in the treatment of advanced hepatocellular carcinoma (HCC). Methods: Patients with advanced HCC, not suitable for resection but with normal major organ functions, were enrolled to receive a therapeutic regimen consisting of intravenous arsenic trioxide (6 mg / m 2 ) administration from days 1-14, and an oral administration of JPLQ formula twice daily from days 1-28. Each cycle was composed of 28 days and treatment could expand up to 4 cycles before evidences of intolerable toxicity or disease progression. Result: One patient had partial response, one had minor response, 15 showed stable disease and 15 (46.9%) had disease progression. Total disease control rate was 53.1%, median survival time was 5.8 months (2-23.9 ms), and time to progression was 4.2 months (1-16.9 months). The incidences of grade 1-3 abdominal distention and nausea/vomiting were 65.6% and 37.5%, respectively. Increases in GGT occurred in 4 patients (2 grade 2, 1 grade 3, and 1 grade 4) and increases in serum creatinine in 2 patients (1 grade 3 and 1 grade 4), respectively. Conclusion: Compared with the single arsenic trioxide treatment reported in past literature, treatment by arsenic trioxide combined with JPLQ showed modestly higher anti-tumor activity and tolerable toxicity in patients with advanced HCC; its manageable toxicity and increased tumor response rate may offer a better treatment regimen, and deserve further investigation. 