Discovering new effective anticancer drugs from natural source have been a field of concern for many researchers. Many researches had reported seaweeds to fill this need. Therefore, this study was performed to screen the anticancer activity of six seaweed species (Actinotrichiafragilis, Cystoseiramyrica, Hormophysa cuneiformis, Laurencia papillosa, Sargassum cinereum, and Turbinaria turbinata) collected from the Red Sea, Hurghada, Egypt. The inhibition of cell viability of the 80 % methanol extract of the six species have been tested on four cancer cell lines (HL60, A549, HCT116 and B16)with MTT assay. The results revealed that H. cuneiformis was the best extract in suppressing HL60, A549, HCT116 with IC50 143.9, 40.97 and 92.6 μg/ml respectively, while the IC50 for B16 was higher than 200 μg/ml. In order to study the anticancer mechanism for the extract, apoptotic body formation test and cell cycle analysis were performed using Hoechst 33342 stain and flow cytometer respectively upon HL60, A549, HCT116 cells. The results showed that H. cuneiformis extract caused DNA damages and rising in the apoptotic body formations for the three cancer cell lines in a dose-dependent manner. Analysis of cell cycle exposed that H. cuneiformis extract could induce cell cycle arrest, which was noticed from increasing the sub-G1 and G2/M phases and decreasing of G0/G1 phase. Thus, the extract suggested anticancer mechanism is through the induction of apoptotic body formation in the cancer cells and arresting in the cell cycle. In conclusion, the extract of H. cuneiformis could be a potential anticancer drug that requires in vivo study for more confirmation. Furthermore, this study about H. cuneiformis