Surgical removal has been accepted as a therapeutic option for hepatocellular carcinoma. However, little is known about the quality of life after hepatectomy for hepatocellular carcinoma. In this report, we describe the risk factors most affecting impaired quality of life after partial hepatectomy in patients with hepatocellular carcinoma.Ninety-six patients who received curative resections 12-60 months previously, answered our original questionnaire, mailed to them. The questions consisted of 14 items concerning physical function, social function, psychological function, physical sensation, and recognition of the disease, with a scoring system of 1, 2, and 3. Based on the pre- and postoperative serum alanine aminotransferase or cholinesterase levels at 3-month intervals during the follow-up period, the changes were classified into three types: those staying in the favorable or unfavorable range at one year (no change, Type 1 or Type 3), and those entering the unfavorable range postoperatively (Type 2).Total quality of life score: the sum of scores to questions 1-12, displayed two peaks of normal distribution. Based on a point of intersection of the two curves: i.e., score of 22, the patients were classified into 2 groups: those with preserved quality of life (n = 75) i.e., total quality of life scores of 12-21, and impaired quality of life, scores of 22 or more (n = 21). Older age (or = 65 y) at hepatectomy, in the course of treatment for recurrence, and Type 2 change of serum cholinesterase level were associated with the impaired quality of life. Multivariate analysis revealed that Type 2 change of serum cholinesterase levels was an independent risk factor for an impaired quality of life. Furthermore, the patients exhibiting Type 2 change of serum cholinesterase levels were clearly impaired in their physical and social functions compared to the other patients. Hepatitis-related or cancer-related factors showed no correlation with the deterioration of the quality of life.The quality of life after hepatectomy in patients with hepatocellular carcinoma was impaired in cases of aged patients, treatment for recurrence, and Type 2 change of the serum cholinesterase level. Postoperative maintenance of protein synthesis including cholinesterase is one measure to preserve a satisfactory quality of life after hepatectomy.