BackgroundColorectal cancer (CRC) is the third most common cancer in the world, with enhancing morbidity and mortality each year. Due to the drug resistance against CRC, the use of novel compounds besides chemotherapy is required. Natural seafood contains large amounts of biologically active substances with new chemical structures and new medicinal activities. The aim of this study was to evaluate the effects of hydroalcoholic extract of Sargassum oligocystom algae on SW742, HT-29, WiDr and CT-26 CRC cell lines and to evaluate the expression of P53 and APC genes using quantitative real time PCR (RT-qPCR). MethodsThe cytotoxicity of S. oligocystom hydroalcoholic extract was determined by MTT and trypan blue methods in six different concentrations including 0.1, 0.2, 0.5, 1, 2 and 4 mg / mL on various CRC cell lines and a control group. The expression of P53 and APC genes in exposure to 2mg/mL of the extract was also evaluated using RT-qPCR. ResultsThe LD50 and LD90 of S. oligocystom included 0.5-1 and > 2mg/mL, respectively mostly affecting SW742 and CT-26 cells. In the trypan blue test, 90% viability and death of cells was observed at 0.1 and 4mg/mL of extract, respectively. The 2mg/mL was a safe cytotoxic concentration. A signi cant viability decrease was observed at concentrations ≥ 1mg/mL (p < 0.001). S. oligocystom extract at 2 mg/mL signi cantly increased the expression of APC being 2.2 fold (p < 0.001) but not P53 gene to be 0.66 fold (p = 0.323) after 24h. ConclusionThese results indicated that the brown algae S. oligocystom extract had signi cant antitumor effects against the SW742, HT-29, WiDr and CT-26 CRC cell lines and especially CT-26, suggesting that it may be a potential candidate for further studies and therefore designing drugs of natural anti-cancer origin. The S. oligocystom had anticancer effect via increase in the APC gene expression.