Objective To investigate the effects of hepatic arterial chemoembolization combined with percutaneous microwave ablation on serum tumor markers and prognosis of patients with liver cancer. Methods A total of 80 patients with liver cancer receiving treatment in Anyang People"s Hospital from October 2021 to October 2023 were included in this study. According to different treatment methods, they were divided into control group (40 cases receiving hepatic arterial chemoembolization) and study group (40 cases receiving hepatic arterial chemoembolization). He was treated with hepatic arterial chemoembolization combined with percutaneous microwave ablation). The short-term efficacy, serum tumor markers, liver function indicators, immune function indicators, complications and prognosis of the two groups were compared 1 month after treatment. Results The total effective rate of the study group (87.50%) was higher than that of the control group (67.50%) (χ2=3.992, P<0.05). After treatment, the levels of tumor markers in both groups decreased, and those in the study group were lower (t=11.520, 35.177, 5.194, all P<0.05). After treatment, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in 2 groups were lower than before treatment, and those in study group were lower (t=7.084, 9.176, both P<0.05). After treatment, the immune function indexes of the two groups were improved compared with those before treatment, and the study group was significantly improved (t=4.740, 7.985, 5.147, all P<0.05). There was no significant difference in the incidence of complications between the two groups (χ2=0.157, P>0.05). One year after treatment, the recurrence rate of the study group was lower than that of the control group (χ2=4.114, P<0.05). Conclusion In the treatment of patients with liver cancer, the combination of hepatic arterial chemoembolization and percutaneous microwave ablation can reduce the level of serum tumor markers, improve liver function and immune function, with definite efficacy, and can reduce the recurrence rate with good safety.