A study on the anti-inflammatory activity of brown alga Sargassum siliquastrum led to the isolation of sargachromanol G (SG). In this study, the anti-inflammatory effect and the action mechanism of SG have been investigated in murine macrophage cell line RAW 264.7. SG dose-dependently inhibited the production of inflammatory markers [nitric oxide (NO), inducible nitric oxide synthase (iNOS), prostaglandin $E_2$ ($PGE_2$), and cyclooxygenase-2 (COX-2)] and pro-inflammatory cytokines [tumor necrosis factor-${alpha}$ (TNF-${alpha}$), interleukin (IL)-$1{eta}$, and IL-6] induced by LPS treatment. To further elucidate the mechanism of this inhibitory effect of SG, we studied LPS-induced nuclear factor-${kappa}B$ (NF-${kappa}B$) activation and mitogen-activated protein kinases (MAPKs) phosphorylation. SG inhibited the phosphorylation $I{kappa}B-{alpha}$ and NF-${kappa}B$ (p65 and p50) and MAPK (ERK1/2, JNK, and p38) in a dose dependent manner. These results suggest that the anti-inflammatory activity of SG results from its modulation of pro-inflammatory cytokines and mediators via the suppression of NF-${kappa}B$ activation and MAPK phosphorylation.