Saccharina japonica is a family member of Phaeophyceae (brown macro-alga) and extensively cultivatedin China, Japan and Korea. Here, the potential anti-cancer effect of n-hexane fraction of S. japonica wasevaluated in SK-Hep1 human hepatocellular carcinoma cells. The N-hexane fraction reduced cell viability andincreased the numbers of apoptotic cells in a both dose- and time-dependent manner. Apoptosis was activatedby both caspase-dependent and independent pathways. The caspase-dependent cell death pathway is mediatedby cell surface death receptors and activated caspase-8 amplified the apoptotic signal either through directactivation of downstream caspase-3 or pro-apoptotic proteins (Bad, Bax and Bak) subsequently leading to therelease of cytochrome c. On the other hand, caspase-independent apoptosis appeared mediated by disruptionof mitochondrial membrane potential and translocation of AIF to the nucleus where they induced chromatincondensation and/or large-scale DNA fragmentation. In addition, the n-hexane fraction induced endoplasmicreticulum (ER)-stress and cell cycle arrest. The results suggested that potential anti-cancer effects of n-hexaneextract from S. japonica on SK-Hep1 cells.