In this study, we investigated the anti-inflammatory effects and mechanisms of Hizikia fusiformis (HF) extracts in lipopolysaccharide (LPS)-induced RAW 264.7 cells. We extracted HF using solvent and sub-critical water techniques. In results, HF extracts inhibited nitric oxide (NO) production in cell-free and LPS-stimulated RAW 264.7 cells. HF210 (extract prepared with sub critical water at 210oC) was most effective. The HF210 extract dose-dependently inhibited inducible nitric oxide synthase expression (iNOS) and nuclear factor kappa (NF-B) p65 translocation from cytosol to the nucleus. Furthermore, HF210 extract dose-dependently inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), Jun N-terminal kinase (JNK), and signal transducers and activators of transcription (STAT)-1in LPS-induced RAW 264.7 cells. Thus, our results suggest that anti-inflammatory effects of HF210 extract showed a noticeable distinction by regulation of multiple signaling pathways in LPS-induced RAW 264.7 cells.