The results of this study confirmed the inhibitory effect of Saccharina japonica hot water extract (SJH) on the inflammatory response when HaCaT keratinocytes were irradiated with UV-B. SJH significantly improved cell viability without cytotoxicity and also reduced the NO content increased by UV-B irradiation. In addition, SJH effectively reduced the mRNA expression of cytokines and chemokines increased by UV-B irradiation, and also reduced the protein expression levels of related factors iNOS and COX-2 through inhibition of Nuclear Factor Kappa B (NF-κB) signaling pathway activation. Additionally, it effectively inhibited the expression of proteins (NLR family pyrin domain containing 3 (NLRP3), Apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), interleukin 1-beta-converting enzyme (Caspase-1), Interleukin(IL)-18, and IL-1β)) related to the NLRP3 signaling pathway, an inflammation-related protein. These research results suggest that SJH can effectively suppress the inflammatory response that can occur due to UV-B irradiation.