Abstract:Background and Aims Conversion therapy offers initially unresectable hepatocellular carcinoma (HCC) patients a chance for curative resection. However, the optimal margin width following conversion remains unclear. This study aimed to evaluate the impact of surgical margin width on prognosis and identify independent prognostic factors in HCC patients undergoing hepatectomy after conversion therapy.Methods A retrospective analysis was performed on 413 patients with initially unresectable HCC who received conversion therapy and underwent radical resection at Cancer Prevention and Control Center of Sun Yat-sen University between February 2015 and June 2022. According to the intraoperatively measured pathological margin, patients were classified into two groups: tumor margin <1 cm and ≥1 cm, and further divided into subgroups with margins of 0 cm, 0.1 cm, and >0.1 cm to compare survival differences among groups. The Kaplan–Meier method and Cox proportional hazards model were used to evaluate disease-free survival (DFS), overall survival (OS), and their influencing factors.Results The 3-year OS and DFS showed no significant difference between the <1 cm and ≥1 cm groups (both P>0.05). However, patients with a 0 cm margin had significantly worse OS than those with a 0.1 cm margin (P=0.048). No significant survival difference was observed in OS and DFS between the 0.1 cm and >0.1 cm groups (both P>0.05). Multivariate analysis identified multiple tumors, poor differentiation, and microvascular invasion as independent adverse prognostic factors for both OS and DFS (all P<0.05), whereas targeted therapy was an independent protective factor for DFS (P=0.014).Conclusion A pathological margin ≥0.1 cm provides comparable survival to wider margins and can be considered a safe threshold for HCC patients undergoing hepatectomy after conversion therapy. The conventional 1 cm margin standard offers no additional benefit. Multiple tumors, poor differentiation, and microvascular invasion predict poor prognosis, while targeted and immunotherapy during conversion may improve long-term outcomes.