Objective To study the expression level of miR-21 in UVB irradiated HaCaT cells and A431 cells. Methods Real-time qPCR was used to examine the expression level of miR-21 in HaCaT cells and A431 cells after 50 J/m2UVB radiation. The possible target genes were predicted by PicTar and performed function categories with Gostat analysis. Results Compared with the HaCaT cells, miR-21 the expression level in A431 cells increased over 4 times. At 2h and 4h after UVB irradiation, the expression level of miR-21 in HaCaT cells were up regulated, and it lowered 2 times at 8 h compared with the control.There was no further change in the expression level of miR-21 after 12 h. While miR-21 expression levels in A431 cells were not changed signifcantly. The results of target prediction and Gostat analysis suggested that PIK3R1, BCL2 and E2F3 were involved in the cell differentiation and cell process. Conclusion miR-21 possibly involved in the pathogenesis of epidermal squamous cell carcinoma and the mechanism of UVB-induced injury.