This study generated a transgenic zebrafish line Tg(k18:Ptmaa-RFP) with overexpression of Prothymosin alpha type a (Ptmaa) in the skin epidermis. Red fluorescence first appears very weakly in the early stage, become stronger and mainly restricted in the nuclei of the epithelial cells from 3 dpf-larvae to adult fish. However, no evident morphological abnormalities were observed. Thus, overexpression of Ptmaa alone is not sufficient to cause disorganized growths or even cancer in zebrafish skin. Molecular and histological evidences showed that Tg(k18:Ptmaa-RFP) embryos have more proliferating cells in the pelvic fins [WT: 3.92 ± 7.15; Tg(k18:Ptmaa-RFP): 38.00 ± 10.87] and thicker skin [WT: 10.98 ± 1.41 μm; Tg(k18:Ptmaa-RFP): 14.02 ± 1.32 μm], indicating that overexpression of Ptmaa can promote proliferation. On the other hand, fewer apoptotic signals were found when Tg(k18:Ptmaa-RFP) embryos were exposed to UVB. Together with quantitative RT-PCR data, we suggest that UVB-induced epidermal cell apoptosis of zebrafish larvae can be attenuated by overexpression of Ptmaa through the enhancement of transcriptions of bcl2 mRNAs. Taken together, we conclude that overexpression of Ptmaa in zebrafish epidermal cells promotes proliferation and attenuates UVB-induced apoptosis but does not cause skin cancer.