Immunotherapy combined with chemotherapy have synergistic effects in multiple malignancies. We aimed to compare the efficacy and safety of toripalimab plus hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, fluorouracil, and leucovorin versus lenvatinib in advanced hepatocellular carcinoma (HCC). We conducted this retrospective study at 3 hospitals in China and eligible patients were 18 years or older and had a primary diagnosis of unresectable HCC with macroscopic vascular invasion and/or extrahepatic spread. These patients were treated with toripalimab plus HAIC or lenvatinib monotherapy. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were overall survival (OS), disease control rate per response evaluation criteria in solid tumors (RECIST) 1.1, and objective response rate (ORR) per RECIST 1.1. The results were compared by Student's test or the chi-square test, and the survival curves were calculated by the Kaplan-Meier method, and propensity-score matching (PSM) was used to reduce bias. A total of 118 patients were recruited for this study: 53 in the TorHAIC group and 65 in the lenvatinib group. We found that the TorHAIC group showed a longer PFS (9.3 [95% CI, 7.81-10.8] vs 4.8 months [95% CI, 3.31-6.29]; hazard ratio [HR] = 0.57, 95% CI, 0.38-0.85;  = .006), a longer OS (17.13 [95% CI, 13.99-20.27] vs 10.1 months [95% CI, 8.14-12.06]; HR = 0.5, 95% CI, 0.31 - 0.81;  = .005), a higher disease control rate (86.8% vs 69.2%,  = .002) and a higher ORR (47.2% vs 9.2%,  < .001) by RECIST criteria than the lenvatinib group. Both toripalimab plus HAIC and lenvatinib had acceptable safety profiles. No treatment-related deaths occurred in this study. In the propensity score-matched cohorts (47 pairs), the outcomes in the TorHAIC group were also better than those in the lenvatinib group ( < .05). Toripalimab plus HAIC was tolerable and effective in advanced HCC and the result needs to be confirmed in the phase III trial.