Background and objective: Patients with hepatocellular carcinoma (HCC) and a high tumor burden, such as those presenting with a tumor diameter of >= 10 cm or/and major portal vein tumor thrombosis (PVTT), generally face a poor prognosis. Sarcopenia is common in this population. Triple therapy combining hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and programmed death receptor-1 (PD-1) inhibitors has shown encouraging outcomes in these patients. This study investigated the association between sarcopenia and the prognosis in patients with high tumor burden HCC patients receiving this triple therapy. Methods: This study included 449 patients with high tumor burden HCC patients who received HAIC-LEN-PD1 triple therapy of from January 2022 to December 2024. Sarcopenia was assessed using the skeletal muscle index (SMI). Propensity score matching (PSM) was used to balance baseline characteristics between groups. Treatment efficacy was evaluated by overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Cox proportional hazards regression analyses were performed to identify independent factors associated with OS and PFS. Results: Totally 449 patients were analyzed, including 131 in the sarcopenia group and 318 in the non-sarcopenia group. After PSM(1:1), 131 patients were matched in each group. Median OS was 12.2 months in the sarcopenia group and 18.1 months in the non-sarcopenia group(hazard ratio [HR]: 1.84; p < 0.001). PFS was also shorter among patients with sarcopenia, with a median of 6.9 months compared with 9.9 months among those without sarcopenia (HR: 1.53; p = 0.002). ECOG PS, and sarcopenia were independent predictors for OS and PFS (p < 0.05). Conclusion: Sarcopenia was associated with an poor prognosis in patients with high tumor burden HCC patients who received HAIC-LEN-PD1 therapy.