Objective  This study is to investigate the correlation between the serum leptin level and the occurrence of hepatocellular carcinoma based on hepatitis B cirrhosis, as well as the clinical features of patients with high Leptin level.  Methods  In this prospective study, totally 232 cases of HCC based on hepatitis B cirrhosis were included, and another 200 age-gender-matched cirrhosis patients with Child-Pugh A liver function was recruited as the pair control group. Serum Leptin level was determined with ELISA. Multivariate logistic regression analysis was performed to investigate the possible related factors for HCC. Results  Among these 432 subjects, totally 95 pairs were obtained and analyzed. The average ages for the HCC and cirrhosis groups were 49.91±9.901 and 50.32±10.759 years, with significant inter-group differences. The male to female ratio was 77/18, and the ratio of Han/ Uyghur/ Kazak ethnicities was 92/2/1. For the HCC group, there were 26 patients (27%) combined with obesity and type II diabetes, and 18 patients (19%) combined with obesity or type II diabetes. For the cirrhosis group, there were 47 patients (49%) combined with obesity and type II diabetes, and 6 patients (6%) combined with obesity or type II diabetes. The multivariate logistic regression analysis involved Leptin, ferritin, CRP, AFP, BMI, and type II diabetes. Conclusion  Serum Leptin level represents the risk factor for HCC based on hepatitis B cirrhosis, and elevated serum Leptin level might be the marker for hepatitis B cirrhosis combined with metabolic factors such as obesity.