Background: This study aimed to investigate the usefulness of a weight-loss program (WLP) in patients with a high body mass index (BMI) prior to liver resection (Hx) for hepatocellular carcinoma (HCC). Methods: Among 445 patients with HCC who underwent initial Hx between 2000 and 2020, 19 with a high BMI (≥25.0) were enrolled in our WLP since 2014. For calorie restriction, the amount of energy consumed was calculated as the standard body weight (SBW) kg × 20–25 kcal/day. Protein mass was calculated as SBW kg × 1.0–1.2 g/day to maintain skeletal muscle mass. Patients also performed both aerobic and resistance exercises. The before-and-after changes were compared, and the effect of WLP on the short- and long-term results was investigated. Results: The average length of WLP was 21 days, and weight loss was successfully achieved in all patients. Body fat mass was reduced during the program, while skeletal muscle mass was maintained. WLP led to improvements in liver function and fibrotic markers, without tumor progression. There were no postoperative complications (≥Clavien–Dindo [CD] III). A retrospective comparison of postoperative outcomes revealed that those in the WLP group showed a significantly shorter operation time and improved postoperative morbidity rate (≥CD III) with decreased postoperative hospital stay. There were no significant differences in long-term prognosis based on participation in the WLP. Conclusions: WLP with multidisciplinary intervention improved short-term outcomes after Hx in patients with HCC and a high BMI.