Objective To analyze the discrepancy between clinical diagnosis and pathological diagnosis in patients with chronic hepatitis B (CHB) and explore more objective criteria of clinical diagnosis. Methods Three hundred and nineteen CHB patients received liver biopsy for pathological assessments were investigated retrospectively in this study. The discrepancy between clinical diagnosis and pathological diagnosis was analyzed. The data were compared using nonparametrie test. Results Based on the standard of pathological diagnosis, accuracies of clinical diagnosis with mild, moderate, severe CHB and cirrhosis were 67.3%, 37.6%, 2.7% and 23.5%, respectively, and the misdiagnose rate of cirrhosis was as high as 93.4 0%. Coincidence rates of clinical diagnosis of fibrosis staging inmild, moderate and severe CHB were 75.0%, 81.7% and 83.8%, respectively, which were relatively high, but was as low as 23.5% in cirrhosis. Levels of alanine aminotransferase (ALT) and total bilirubin(TBil) were not gradually increasing with stages of mild, moderate, severe and cirrhosis in clinical or pathological diagnosis. Conclusions There are differences between clinical diagnosis and pathological diagnosis. The accuracies of clinical diagnosis are low in patients with severe hepatitis and cirrhosis. It's better to make diagnosis based on liver biopsy so that to improve the diagnose accuracy.