Introduction: Pleurotus citrinopileatus is a mushroom with n-number of biomolecules expressing both nutraceutical and pharmaceutical qualities. In recent years, there are many medicinal properties of the mushroom brought to light, be it the biomolecules that inhibits fat-induced weight gain; cancer treatments for hepatoma, colon or HIV-1 reverse transcriptase inhibitory activity by novel lectins present in it. Objective: The present study is to find the degree of cell damage in HepG2 cancer cell lines caused by the extracts of Pleurotus citrinopileatus. Method: Herein, we are going to compare the level of cell damage caused by acetone, ethanol and aqueous extracts of Pleurotus citrinopileatus using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Result: Acetone extracts of the mushroom showed higher cell damage in HepG2 cell line, indicated by MTT assay with the half-maximal inhibitory concentration (IC50) value of 37.03__ampersandsignmicro;g/ml, compared to the ethanolic and aqueous extracts of Pleurotus citrinopileatus. Conclusion: The acetone extract appears to possess biologically active compounds that might help reduce the viable cancer cells. If used as an adjuvant drug with cisplatin can reduce the effects caused by it and activate P53 action. Novelty: Further study on the biomolecules present in oyster mushrooms can give us an insight into the apoptotic behavior of cancer cells.