This study investigated the inhibitory effect of an ultrasonic water extract from Sargassum horneri (UKSHW) against ultraviolet B (UVB)-induced inflammatory response in HaCaT cells, a human keratinocyte. UKSHW increased the cell viability by reducing the production of nitric oxide (NO) in UVB-irradiated HaCaT cells. Also, UKSHW significantly reduced the secretion of inflammatory cytokines (interleukin (IL)-6 and -8, tumor necrosis factor (TNF)-a) and chemokines (macrophagederived chemokine (MDC) and thymus and activation-regulated chemokine (TARC)) by inhibiting the activation of mitogenactivated protein kinase (MAPK) and nuclear factor (NF)κB signaling in UVB-irradiated HaCaT cells. With these results, the present study suggests that UKSHW inhibited the inflammatory response in UVB-irradiated HaCaT cells.