Objective To explore the clinical significance of peripheral blood CD27+B cell percentage in patients with different HBV-related disease progressions. Methods 20 patients with chronic hepatitis B, 23 patients with hepatitis Bassociated liver cirrhosis and 21 patients with hepatitis B-related hepatocellular carcinoma treated from February 2016 to February 2017 in our hospital were selected. 25 healthy check-ups were selected as control group. The CD27+ B cell percentage as well as IgM and IgD expression of humoral immunity for each group was compared. Results Based on the TCD27+ B cell percentage, the healthy check-ups accounted for (5.17±0.38)%, the chronic hepatitis B patients for (4.53±0.21)%, hepatitis B- associated liver cirrhosis patients for (2.23±0.12)% and the hepatitis B-related hepatocellular carcinoma patients for (0.55±0.04)%, it was known that the CD27+ B cell percentage for the HBV-related patients were significantly lower than control group (P<0.05), the severer the disease was, the lower the CD27+ B cell percentage was; the expression of IgM and IgD for HBV-related patients were significantly higher than control group (P<0.05), the severer the disease was, the higher the IgM and IgD expression was. Conclusion With the severer HBV-related disease,the CD27+ B cell percentage is lower while the IgM and IgD expression is higher, which it indicates the CD27+ B cells have a close correlation with the HBV-related patients. The monitoring of CD27+ B cell is used to evaluate the patient’s immune system and provide the treatment guidance in clinical practice.