To explore the clinical efficacy and security analysis of DEB-TACE combined with carrelizumab in the therapy of advanced liver cancer. This study was prospectively designed. Using a random number table method, 96 patients with advanced liver cancer hospitalized from August 2022 to August 2023 were divided into the DT group (DEB-TACE treatment, n = 48) and the DT-C group (on the basis of the DT group, receiving carrelizumab infusion via hepatic artery, n = 48). The changes of therapeutic effect, serum tumor markers, T lymphocyte subsets, overall survival (OS) and progression-free survival (PFS) and the adverse effect were observed. The ORR and DCR of the DT-C group were higher than that of the DT group (P < 0.05). After 1 month of treatment, CD3+, CD4+ and CD4+/CD8+ were increased and the DT-C group was higher than the DT group (P < 0.001). The CD8+ decreased after 1 month of treatment, and the CD8+ in the DT-C group was significantly lower than that in the DT group (P < 0.001). AFP and PIVKA-II decreased after 1 month of treatment, and the DT-C group was lower than the DT group (P < 0.001). The overall survival (OS) (2-year survival rate 33.33%) and progression-free survival (PFS) (2-year survival rate 18.75%) of the DT-C group were higher than those of the DT group (P < 0.05). There was no difference in the adverse reaction incidence (P > 0.05). DEB-TACE combined with trans arterial infusion of carrelizumab is safe and effective in the treatment of advanced liver cancer. Compared with DEB-TACE alone, this combination therapy results in higher CD3+, CD4+, and CD4+/CD8+ levels, as well as reduced CD8+, AFP, and PIVKA-II levels.