Objective: To investigate the clinical efficacy and safety of transarterial chemoembolization(TACE) combined with targeted therapy and PD1 inhibitors in patients with advanced liver cancer. Methods: This was a retrospective study. A total of 120 patients with advanced primary liver cancer admitted to Affiliated Hospital of Hebei University were randomly divided into two groups, with 60 patients in each group from May 2020 to May 2023. Patients in the control group received conventional TACE, and those in the experimental group received 200 mg camrelizumab once every 21 days and oral lenvatinib mesylate capsules once daily in addition to TACE. Compared the clinical efficacy, levels of tumor markers, T lymphocyte subsets, and adverse drug reactions after treatment and the improvement of quality of life(QOL) before and after treatment between the two groups of patients. Results: The overall response rate(ORR) was 80% in the experimental group and 62% in the control group, and the difference was statistically significant(p=0.03); the incidence of adverse reactions was 28% in the experimental group and 25% in the control group, with no significant difference between the two groups(p=0.68); the improvement rate of QOL score was significantly increased(p=0.03) and the deterioration rate was significantly decreased(p=0.01) in the experimental group compared with those in the control group, respectively. Conclusion: TACE combined with targeted therapy and PD1 inhibitors is significantly effective to improve the cellular immune function with no significant increase in the incidence of adverse reactions, making it an effective and safe treatment option for patients with liver cancer.