Current research in drug discovery from medicinal plants involves the identification of safe and inexpensive lead molecule towards diseases. Cancer is a second major national burden leading to cause death. Reducing the nation"s cancer burden is a great challenge to win the "War of cancer". During the last decades, numerous novel compounds have been found from marine organisms with interesting pharmaceutical activities. Hence, a novel brown algae, Sargassum ilicifolium (Turner) C.Agardh belonging to Sargassaceae family has selected and the study was aimed to investigate the in vitro anti-proliferative activity of ethanolic extract and chloroform fraction of Sargassum ilicifolium (Turner) C.Agardh. against colon cancer (HT-29) and lung cancer (A549) cell lines. Extraction of seaweed using 70% ethanol and fractionated with various solvents. Based on phytochemical screening, chloroform fraction was selected, then it was subjected to GC-MS analysis. The 70% ethanolic exract and chloroform fraction were selected to in vitro MTT cell line assay using colon cancer cell line (HT-29) and lung cancer cell line (A549). The GC-MS analysis report confirmed the presence of 21 compounds and in the the invitro assay, IC50value showed the effective anti-proliferative activity against colon and lung cancer cell lines. The results of the present study proved the anti-proliferative effect of Sargassum ilicifolium. Further, the active biomolecule in the fraction has to be isolated and charecterized the formulated product subjected to in vivo study to strengthen the anticancer activity. Keywords : Antiproliferative effect, colon cancer, lung cancer, Sargassum ilicifolium, GC-MS analysis