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Objective: This study aimed to determine the clinical effect of arterial chemoembolization transcatheter (TACE) combined with radiofrequency ablation during the clinical treatment of large hepatocellular carcinoma. Methods: A total of 82 patients with large hepatocellular carcinoma were selected as experimental subjects. These patients received treatment at our hospital from May 2015 to January 2017. Digital parity method was used to divide patients with large hepatocellular carcinoma into two groups. For the control group (41 patients), TACE was adopted for the clinical treatment of large hepatocellular carcinoma. For the observation group (41 patients), TACE combined with Radiofrequency Ablation (RFA) was utilized. Finally, the two groups of patients with large hepatocellular carcinoma were compared in terms of disease treatment effect, treatment satisfaction, liver-function-related indicator, and immune function. Results: The total effective rate of patients with large hepatocellular carcinoma in the observation group (97.56%) exhibited significant improvement compared with that of patients in the control group (65.85%) (P<0.05). The treatment satisfaction of patients in the observation group (97.56%) was significantly higher than that of patients in the control group (68.29%) (P<0.05). Furthermore, the liverfunction-related index of patients in the observation group displayed significant improvement compared with that of patients in the control group (P<0.05). The immune function of patients in the observation group also showed significant improvement compared with that of patients in the control group (P<0.05). Conclusion: During the clinical treatment of large hepatocellular carcinoma, TACE combined with RFA for clinical treatment can improve the treatment efficacy, immune function, and liver function index of patients, thereby improving the prognostic ability of patients with large hepatocellular carcinoma.