This research is aimed to develop marine resources which are focused on the phytochemistry profile and exploration of seaweed macroalgae Sargassum polycystum as a potential anti-colorectal and anti-lung cancer agents. Seaweed macroalgae S. polycystum collected from Lengkuas Beach, Tanjung Pandan, Province of Bangka-Belitung, South Sumatera, Indonesia, were extracted in organic solvent of n-hexane (Hex), ethyl acetate (EA), chloroform (CHCl3), and ethanol (ET), respectively. The concentrated extract of Hex, EA, CHCl3, and ET was then analyzed by thin-layer chromatography. Phytochemistry test of the extracts was conducted to identify the secondary metabolites containing in the seaweed macroalgae. Furthermore, cytotoxic activity of Hex, EA, CHCl3, and ET extracts of S. polycystum was evaluated against colon HCT-116 and lung-A549 cancer cells by MTT cell proliferation assay. Phytochemistry profile of the concentrated extracts of S. polycystum showed the positive result for secondary metabolites of steroid, tannin, alkaloid, triterpenoid, and glycoside. Concentrated extracts of Sargassum sp. exhibited cytotoxicity against colon HCT-116 and lung-A549 cells with median inhibitory concentration ranging from 21.3 μg/mL to 33.4 μg/mL. These results are suggesting that seaweed macroalgae S. polycystum as a potent candidate for the new anti-colorectal and anti-lung cancer agents.