Objective To analyze the safety of mesohepatectomy and long term outcomes for patients of centrally located large hepatocellular carcinoma.Methods 25 consecutive mesohepatectomies were performed for primary hepatocellular carcinoma (diameter ＞ 5 cm) from August 2005 to December 2011.There were 24 males and 1 female with average age of 44.8 (range 33 to 67) years.Recurrence-free and overall survival rates were analyzed by the Kaplan-Meier method.Results The diagnosis of primary hepatocellular carcinoma was pathologically established in all patients.The median tumour size was 8.1 (5.0-15.0) cm.Serum hepatitis B surface antigen was detected in 22 patients,the preoperative results of serum AFP level was higher than 20 μg/μl in 16 patients.Child-Pugh grade was A in all patients.During transaction,23 patients required continuous or intermittent total portal triad clamping,one patient required hemi-occlusion of the afferent blood flow extra-hepatically.The median clamping time was 30.3 (12-70) min.The median intra-operative blood loss was 266.8 (50-600) ml.The median length of operation was 191.3 (135-358) min.14 patients had blood transfusion.The median hospital stay was 20.2 (9-37) days.The overall morbidity rate was 44％ (11/25).No patient died post-operatively.25 patients were followed-up from 3 to 78 months (average 28 months),the recurrence-free and overall 1,3year's survival rates were 63.7％,26.7％ and 86.4％,38.7％ respectively.Conclusions Mesohepatectomy is a feasible and effective surgical treatment for centrally located large hepatocellular carcinoma,especially for patients with chronic hepatitis or cirrhosis.