To investigate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) combined with anti-PD1 monoclonal antibody (anti-PD1 mAb) in advanced primary liver cancer with microvascular invasion. Patients were retrospectively classified into two cohorts, namely the HAIC-PD1 group and the HAIC group, based on their treatment regimen. Clinical data were collected from January 2018 to December 2021 for a cohort of 61 patients with advanced primary liver cancer who underwent combination therapy of HAIC-mFOLFOX6 and anti-PD1 monoclonal antibody (HAIC-PD1 group), alongside a separate cohort of 95 patients who received HAIC-mFOLFOX6(HAIC group) alone. The above-mentioned 156 patients were matched by propensity score to obtain the overall cohort and the matched cohort. The differences in overall survival(OS) and progression-free survival(PFS) were compared between the groups and the tumor treatment response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Furthermore, a comparison of objective response rate (ORR) and disease control rate (DCR) was conducted between the overall cohort and the matched cohort. Univariate and multivariate analyses were employed to identify independent risk factors affecting OS and PFS. In both the overall cohort and the matched cohort, the HAIC-PD1 group demonstrated superior OS and PFS outcomes compared to the simple HAIC group (P<0.0001). However, no significant differences were observed in ORR or DCR between the HAIC-PD1 group and the HAIC group. Multivariate analysis revealed that ALBI grade and treatment group served as predictive factors for OS, while extrahepatic metastasis along with the treatment group acted as independent risk factors for PFS. Notably, combining HAIC with anti-PD1 monoclonal antibody therapy exhibited more pronounced survival benefits than HAIC alone in patients with advanced HCC featuring vascular invasion; moreover, both approaches displayed similar efficacy in controlling tumor progression.