To analyze the value of soluble intercellular adhesion molecule-1 (sICAM-1), alpha fetoprotein (AFP), and aspartate aminotransferase (AST)/platelet (PLT) ratio index (APRI) in predicting the prognostic survival of patients with primary liver cancer after radiofrequency ablation (RFA). The data of 115 patients with primary liver cancer admitted to our hospital from June 2016 to June 2018 were retrospectively analyzed as the research group, and 120 healthy people who were examined during the same period were selected as the control group. Multivariate logistic regression analysis was used to analyze the risk factors that affect the prognostic survival of patients with primary liver cancer treated with RFA. Receiver operating characteristic (ROC) curve was used to analyze the value of serum sICAM-1, AFP, and APRI levels in predicting the prognostic survival of patients with primary liver cancer after RFA. The levels of sICAM-1, AFP, and APRI in the control group were significantly lower than those in the study group, and the difference between the 2 groups was statistically significant (P<0.05). After 115 patients were followed up for 2 years, the 2-year survival rate was 55.65% (64/115). Multivariate logistic regression showed that the clinical stage: III + IV, extrahepatic metastasis, abnormal increasing in sICAM-1, AFP, and APRI levels, were independent risk factors affecting the prognosis survival of hepatocellular carcinoma (HCC) patients after RFA treatment (P<0.05). The ROC curve showed that the areas under the curve of sICAM-1, AFP, APRI, and their combination in predicting the prognosis survival of HCC patients after RFA treatment were 0.693, 0.828, 0.901, and 0.947, respectively, with the area under the curve of the combination being the largest. ICMS-1, AFP, and APRI are closely related to the RFA treatment and prognosis of HCC patients. In clinic, individualized treatment plans can be formulated based on these levels, which can contribute to prolonging the survival of patients.