Objective To investigate the affection on inner environment of patients with severe viral hepatitis using plasma exchange (PE) and avoid the complication correlated with PE. Methods A total of 62 patients with severe viral hepatitis were enrolled for treatment with PE. Function of liver and kidney and serum electrolyte, complement and complement activity, cytokines level of TNF-α and IL-6, international normalized ratio were determined, and test data of the subsequent day after PE was compared with the data before treatment. The form of peripheral blood RBC was also observed before and after PE. Results The liver function index of the patients was significant improved and hyponatremia was corrected after PE therapy. Serum calcium level was reduced, so it was essential for supplement of calcium during PE. Serum concentration of complement C3 and C4 was increased, but serum level of TNF-α and IL-6 was decreased. Thromboplastic function was improved after PE. The configuration of peripheral blood RBC remained stable. Conclusion Plasma exchange therapy can recover the liver function and improve the thromboplastic mechanism, and decrease the abnormal immunological reaction of patients with severe viral hepatitis, and maintain stabilization of inner environment. The PE therapy is safe and effective for severe viral hepatitis.