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Purpose: To investigate the effect of Yugan Sanjie decoction on the expressions of regulatory T cells (Tregs), serum P21 protein and vascular endothelial growth factor (VEGF) in mice with hepatocellular carcinoma. Methods: A total of forty specific-pathogen-free (SPF) Kunming mice were randomly assigned to four groups of 10 mice each. Except for normal control group, the other three groups were transfected with hepatoma-22 (H22) cells to establish a mouse model of liver cancer. Mice in the cyclophosphamide group was given cyclophosphamide at a dose of 20 mg/kg daily intragastrically, while those in decoction group were treated with Yugan Sanjie decoction (0.4 ml/kg/day) intraperitoneally. After 30 days of treatment, serum levels of CD4+Th17, CD4+CD25+ Treg, Th17/Treg, TNF-α, and VEGF were determined. Results: There was lower serum level of CD4+Th17 in the decoction group than in negative control and cyclophosphamide groups (p < 0.05). However, higher serum levels of CD4+CD25+ Treg and Th17/Treg were seen in the decoction group, relative to the negative control and cyclophosphamide groups (p < 0.05). Serum TNF-α was also markedly elevated in decoction group, when compared with negative control and cyclophosphamide groups (p < 0.05). Serum VEGF was markedly lower in decoction group than in negative control and cyclophosphamide groups, and was appreciably lower in cyclophosphamide group than in negative control group (p < 0.05). Conclusion: Yugan Sanjie decoction effectively alleviates clinical symptoms of LC, and improves immune function of mice by regulating serum levels of T lymphocytes. These findings provide scientific support for a new treatment strategy. [ABSTRACT FROM AUTHOR]