Abstract： Objective： To observe the efficacy-enhancing and toxic-reducing effects of Jianpi Shugan Prescription in targeted therapy combined with immunotherapy for advanced hepatocellular carcinoma (HCC). Methods： A total of 56 cases of patients with advanced HCC were selected and divided into the control group and the observation group according to the random number table method，with 28 cases in each group. Both groups were treated with transcatheter TACE for one cycle； the observation group was treated with modified Jianpi Shugan Prescription， Lenvatinib Mesylate Capsules and Tireilizumab； the control group was treated with Lenvatinib Mesylate Capsules and Tireilizumab. Both groups were treated continuously for 12 weeks. Adverse reactions， quality of life scores， objective response rate (ORR)， disease control rate (DCR) and the levels of γ-glutamyl transferase isoenzyme II (GGT-II)，alpha fetoprotein (AFP) and abnormal prothrombin (APT) in serum were compared between the two groups. The one-year and two-year survival rates in the two groups were followed up. Results：The one-year survival rate in the observation group was 85.71%，which was higher than that of 53.57% in the control group (P＜0.05). The two-year survival rate in the observation group was 50.00%， higher than that of 17.86% in the control group (P＜0.05). The incidence of fever， nausea and vomiting and myelosuppression in the observation group was lower than that in the control group (P＜0.05). After 6 and 12 weeks of treatment，the quality of life (QOL) scores in the two groups were increased when compared with those before treatment (P＜0.05)， and the QOL score in the observation group was higher than that in the control group at the same time point (P＜0.05). After 12 weeks of treatment， the ORR and DCR in the observation group were 50.00% and 82.14% respectively， which were higher than those of 17.86% and 50.00% respectively in the control group (P＜0.05). After treatment， the levels of GGT-II， AFP and APT in serum in the two groups were reduced when compared with those before treatment (P＜0.05)，and the levels of GGT-II，AFP and APT in serum in the observation group were lower than those in the control group (P＜0.05). Conclusion： Jianpi Shugan Prescription has obvious efficacy-enhancing and toxic-reducing effects in targeted therapy combined with immunotherapy for advanced HCC，which can increase survival rates of patients，improve their quality of life，and down-regulate the levels of GGT-II，AFP and APT in serum.