This study comprehensively investigates the photoprotective effects of aloin against UVB-induced damage in HaCaT cells, elucidating its antioxidant capacity and its role in preventing cellular apoptosis. The proteomic effect of 50 μg/mL aloin on HaCaT cell damage induced by UVB was evaluated through comparative protein expression. Compared to control cells, UVB irradiation significantly altered protein expression in HaCaT cells, with 64 proteins upregulated and 236 proteins downregulated. In cells treated with both UVB and aloin, 79 proteins were upregulated and 84 proteins were downregulated compared to the UVB-only group. Proteomic analysis showed that aloin modulated the expression of proteins involved in critical signaling pathways, including PI3K-Akt, p53, TGF-β and pathways in cancer, promoting cell survival. Aloin upregulated proteins associated with cell cycle regula-tion and antioxidant responses, such as CCND3, GSTM4, GNA12, SKIL, YWHAZ, and PKN3 while downregulating pro-apoptotic protein FOXO3.