〔Abstract〕 The endoplasmic reticulum is one of the most prominent membranous organelles that plays a significant role in maintaining intracellular homeostasis. Specific internal or external stimulus leading to the accumulation of unfolded or misfolded proteins, alteration in intracellular calcium levels, or disruptions in redox homeostasis will trigger ER dysfunction and, ultimately, endoplasmic reticulum stress（ERS). Physiologically, ERS is involved in maintaining the homeostasis of the epidermal skin barrier. Ultraviolet B (UVB) induces epidermal ERS, following the activation of a variety of physiological and pathological processes. It participates in the physiological processes of epidermal barrier homeostasis and keratinocyte differentiation, and also contributes to pathological processes such as UVB-induced skin inflammation and keratinocyte apoptosis leading to skin damage. Therefore, ERS is expected to become a therapeutic target for UVB-mediated skin-related diseases. Currently, the clinical potential of modulating UVB-induced keratinocyte ERS through the use of antioxidants, NF-κB inhibitors, and ER Ca 2+ regulators has been increasingly recognized. This review focuses on the mechanisms underlying UVB-induced skin damage, the molecular mechanisms of UVB-induced keratinocyte ERS, and the current progress of ERS-targeting drugs in UVB-induced skin damage, providing new insights into ERS’s roles in UVB-induced skin damage and novel therapeutic strategies targeting ERS for the clinical treatment of UVB-induced skin damage.