Abstract: Objective: To investigate the efficacy of natural killer cells(NK cells) assisted radio frequency ablation on patients with liver cancer, and to analyze its influence on tumor markers, T cell subsets, interferon γ(IFN-γ) and survival rate. Methods: A total of 82 patients with liver cancer admitted to Huairou Hospital, Beijing Chaoyang Hospital, Capital Medical University from January 2018 to June 2020 were selected as the research subjects and randomly divided into observation group and control group, with 41 cases in each group. The control group was treated with laparoscopic radio frequency ablation, and the observation group was treated with NK cells assisted laparoscopic radio frequency ablation. Clinical efficacy, survival, serum tumor markers cytokeratin 19(CK19), alpha-fetoprotein(AFP), paternal expression gene 10(PEG10), immune indicators CD4⁺T cells, CD4⁺/CD8⁺, total B lymphocytes, NK cells, NK cell-related to immune factors interleukin-12(IL-12), interleukin-10(IL-10), interferon-γ(IFN-γ), and functional assessmen of cancer therapy-gauge(FACT-G) scores. ^Results: There was no significant difference in the total effective rate between the observation group(70.73%) and the con-trol group(58.54%) at one month after operation(P＞0.05). The levels of serum CK19, AFP, PEG10 and IL-10 in the observation group were all lower than those in the control group at one month after operation. The levels of CD4⁺T cells, CD4⁺/CD8⁺, the total B lymphocytes, NK cells, as well as serum IL-12 and IFN-γ levels in the observation group were higher than those in the control group(P＜0.05). The scores of FACT-G in all dimensions in the observation group were all higher than those in the control group at 6 months after operation(P＜0.05). The median overall survival time(OS) and median progression-free survival time(PFS) in the observation group were 16 months and 12 months, respectively, while the median OS and median PFS in the control group were 12 months and 8 months, respectively(both P＜0.001). Conclusion: NK assisted radio frequency ablation therapy for liver cancer has certain clinical efficacy, which can correct the disorder of T lymphocyte subsets, enhance the immune function of the body, regulate the level of NK cell-related immune factors, and improve the prognosis and quality of life of patients.