Management of multinodular hepatocellular carcinoma (HCC) in the intermediate Barcelona Clinic Liver Cancer (BCLC)-B stage is controversial. The aim of the present study as to identify the subgroup of patients with BCLC-B HCC who could benefit from liver resection. The present study retrospectively analyzed the outcomes of 65 patients (training cohort) who underwent liver resection for multinodular BCLC-B HCC. Cox's regression analysis was conducted to identify the independent prognostic factors for overall survival and to develop the prognostic score. As some authors have reported that maximum tumor size (cm) plus tumor number (N+S) is a prognostic factor in patients with BCLC-B HCC who undergo chemoembolization, the usefulness of this factor in patients who underwent liver resection was also evaluated. Subsequently, the validity of the prognostic score was assessed in an independent validation cohort (n=132). Multivariate analysis revealed that positivity for hepatitis C virus antibody (HCV-ab), platelet count ≤1010/l, N+S >8, and des-γ-carboxy prothrombin (DCP) >400 mAU/ml were independent prognostic factors for overall survival. The prognostic score differentiated two groups (≤2, ≥3) with distinct outcomes (median survival time 68.3 months vs. 29.1 months; P<0.0001). This result was confirmed in an external validation cohort. Therefore, surgery can promote long-term survival in patients with multinodular HCC although the indications for surgery are limited. HCV-Ab status, preoperative platelet count, DCP level and N+S may be useful for patient selection.