Different natural products including lichens, have been using in traditional medicine around the world since the old days. The lichens genera of Graphis and Parmotrema have a great usage in folklore medicine. The Initially, the hydroalcoholic extracts of mangrove associated lichens, Graphis ajarekarii and Parmotrema tinctorum were prepared and were used to get different fractions using n-hexane, chloroform, ethyl acetate, acetone and methanol. The prepared extracts was evaluated for cytotoxicity using Sulforhodamine B (SRB) assay on different cell lines such as MDA-MB-231, SW620, HeLa, FADU, A549, SKOV3 and in vitro toxicity studies using normal human cell line i.e., Normal Human Mammary Epithelial (NHME). Among all the tested extracts, the ethyl acetate extract from G. ajarekarii (Ga-EA) and P. tinctorum (Pt-EA) were active against all tested cancer cells. The SRB assay revealed that Ga-EA and Pt-EA (100 µg/mL) has good inhibitory profile towards SW620 with 70.51 and 75.18%, than that of the doxorubicin (10 µg/mL, 66.71%). Also, the all the extracts from G. ajarekarii and P. tinctorum were found to be inactive against NHME indicates non-toxic. Hence, this study revealed that G. ajarekarii and P. tinctorum has an aptitude to act against cancer.