OBJECTIVE To investigate the inhibiton of polypeptide from Chlamys farreri (PCF) on UVA-induced HaCaT cells apoptosis through p38 mitogen activated protein kinase (MAPK) pathway and caspase-3.METHODS Experiments were divided into six groups: control group, UVA model group, UVA+5.68 mmol·L~ -1 vitamine C positive control group, UVA+5.69 mmol·L~ -1 PCF group, UVA+2.84 mmol·L~ -1 PCF group, UVA+1.42 mmol·L~ -1 PCF group. UVA-induced apoptotic model of HaCaT cells was established by orthogonal design. Using agarose gel electrophoresis, the effects of PCF, p38 MAPK inhibitor SB203580 and caspase-3 inhibitor Ac-DEVD-CHO on UVA-induced apoptosis were investigated. Expression levels of p38 MAPK and phosphorylated p38 MAPK were determined by Western blot analysis. Caspase-3 activity was assayed by flow cytometry.RESULTS PCF significantly protected UVA-induced apoptosis. SB203580 and Ac-DEVD-CHO had inhibitory effects on UVA-induced apoptosis of HaCaT cells. PCF inhibited UVA-induced phosphorylation of p38 MAPK and activation of caspase-3 on a dose-dependented manner.CONCLUSION PCF can protect HaCaT cells from UVA-induced apoptosis. Its inhibitory effect on apoptosis may attribute to inhibition of activation of p38 MAPK and caspase-3.