Abstract: Objective To study the therapeutic effects of S-adenosyl methionine on patients with drug induced cholestatic liver disease associated with depression or anxiety. Methods Total of 38 patients with different causes of drug induced cholestatic liver diseases accompanying with depression or anxiety were selected and treated with intravenous use of S-adenosyl methionine 1.0 g for 2 weeks. Then, Zung’s SDS/SAS assessment were applied to compare the therapeutic effects of these groups. Results The symptoms of depression or anxiety in patients with Chinese traditional drug as well as antibiotics and statins drug induced liver cholestasis improved significantly after treatment with S-adenosyl methionine (P = 0.001, 0.011, 0.018, respectively), however, there seemed no change in anti-neoplasm drugs induced liver cholestasis. Conclusions S-adenosyl methionine plays a dual role of liver protection and anti-depressants in patients with Chinese traditional drug as well as antibiotics and statins drug induced cholestatic liver disease associated with depression or anxiety, which will create a broad application in treating patients with “bio - psycho” diseases.