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Our liver if vulnerable for various chemicals as well as drugs and infectious agents, but truly hepatoprotective medication is not available till today. It is necessary to find out substances which may able to protect the liver. The present cross-sectional study was undertaken to evaluate the hepatoprotective effect of oyster mushroom. This study was carried out during the period of 3rd November 2013 to 10th March 2014 with the help of National Mushroom Development and Extension Centre, Sobhanbag, Savar, Dhaka. Total 33 subjects aged from 31 to 75 years irrespective of sex were included in the study. The serum level of hepatocellular enzymes like AST, ALT, ALP, LDH and Bilirubin were estimated after two months supplementation of 50 gms of fresh oyster mushroom each day. The feeding of 50 grams fresh oyster mushroom significantly reduced the serum levels of AST, ALT, ALP, and LDH. There also a non-significant small reduction of serum bilirubin observed in human volunteers. Findings of the study suggest that oyster mushroom may be helpful for the protection of human liver.