Objective To investigate the clinical effect of plasma exchange in the treatment of chronic severe hepatitis B. Methods 181 patients with chronic severe hepatitis B treated in our hospital from January 2010 to October 2016 were retrospectively analyzed. They were randomly divided into control group (n=85) and observation group (n=96). The control group received routine medical treatment , The observation group was treated with routine medical treatment combined with plasma exchange. The liver and kidney function, blood coagulation index and the effective rate of the two groups were observed. Results The improvement rate of the control group was 82.35%, the improvement rate of the observation group was 93.75%, the difference between the two groups was statistically significant (P <0.05); observation group liver function and coagulation improvement (P<0.05), and the difference was statistically significant (P<0.05). Conclusion Plasma exchange for chronic severe hepatitis B can not only improve the laboratory indexes of patients, but also improve the improvement rate of treatment. It has a good effect and is worth popularizing in clinic.