OBJECTIVE: To evaluate the effect of FOLFOX-HAIC combined with PD-1 inhibitor immunotherapy on the survival of patients with advanced hepatocellular carcinoma (HCC). METHOD: This retrospective study analyzed 137 patients with advanced HCC, of which 71 received FOLFOX-HAIC chemotherapy (control group) and 66 received FOLFOX-HAIC combined with PD-1 inhibitors (research group) between January 2020 and August 2021. Propensity score matching (PSM) was employed to account for confounding variables. Cox regression analysis was utilized to identify independent risk factors that sabotaged patients' survival, and Kaplan-Meier curves were applied to demonstrate patients' overall survival (OS). RESULTS: A significantly higher disease control rate (DCR) was observed in the research group than that in the control group (77.27% vs. 60.56%, P = 0.035). Prior to PSM analysis, the OS of patients in the research group was calculated to be 25 months, which was significantly higher than the 14 months in the control group (P = 0.015). While post PSM analysis, the median OS turned out to be 27 months in the research group, still significantly higher in comparison to the control group (P = 0.002), whose OS was 14 months. By multivariate analysis, the maximum tumor diameter, Eastern Cooperative Oncology Group Performance Status score, and treatment regimen were identified as independent factors affecting patients' prognosis. CONCLUSION: FOLFOX-HAIC combined with PD-1 inhibitor immunotherapy can significantly prolong the survival in patients with advanced HCC. Apparently, this combined therapy is advantageous at extending patient's survival time in comparison to the use of FOLFOX-HAIC therapy alone.