For patients with gastrointestinal stromal tumors (GISTs) and liver metastases, there is still debate about whether radiofrequency ablation (RFA) or hepatectomy is preferable. The present study aimed to compare the clinical outcomes of RFA with hepatectomy in patients with GISTs and liver metastases. The present retrospective study consisted of a cohort of 43 patients who had been diagnosed with liver metastases from GISTs between January 2010 and December 2022. The study included 18 patients who received RFA combined with tyrosine kinase inhibitor (TKI) therapy (RFA group) and 25 patients who underwent hepatectomy combined with TKI therapy (hepatectomy group). For the patients with liver metastases, the progression-free survival (PFS) rates at 1, 3 and 5 years were 66.5, 38.2 and 33.9%, respectively. Notably, patients in the hepatectomy group exhibited significantly improved PFS times compared with those in the RFA group (median PFS, 42.7 months vs. 14.3 months; P=0.034). Furthermore, the time to imatinib treatment failure (TTF) was notably improved in the hepatectomy group compared with that in the RFA group, and this difference was statistically significant (median TTF, 71.1 vs. 38.0 months; P=0.041). However, the overall survival (OS) times of patients who received RFA and those who had hepatectomy did not differ significantly (median OS, not reached vs. not reached, P=0.120). There was no statistically significant distinction in PFS and TTF between patients who underwent hepatectomy combined with postoperative TKI and those who underwent hepatectomy combined with perioperative TKI (median PFS, 29.5 vs. not reached; P=0.520; median TTF, 66.4 months vs. 71.1 months; P=0.430). The univariate and multivariate analyses consistently identified the sole prognostic factor affecting PFS as hepatectomy combined with TKI therapy (hazard ratio, 0.379; 95% CI, 0.159-0.899; P=0.028). In conclusion, hepatectomy combined with TKI therapy improved prognosis for patients with liver metastases to a greater extent than RFA combined with TKI therapy. For this type of patient, hepatectomy may be a preferable option.