Objective：To investigate the effects of interleukin-31（IL-31） or tacrolimus on expression of neurotrophin-4（NT4） in human Hacat cells. Methods：Human keratinocyte cell line（Hacat cells） was cultured and treated with different concentrations of tacrolimus and cell proliferation was determined by the MTT assay. Cultured HaCaT cells were treated with IL-31 alone or in combi－nation with tacrolimus for 24 h. Real-time PCR was used to detect the mRNA of NT4. Levels of NT4 in the culture supernant were measured with ELISA. Results：Tacrolimus with low concentration（10，100） ng/ml had mild effect on cell proliferation（P >0.05），while that with high concentration（1 000 ng/ml） inhibited cell proliferation（P=0.002）. Levels of NT4 in the culture supernant and NT4 mRNA expression were significantly increased in the presence of IL-31. Levels of NT4 in the culture supernant and NT4mRNA expression were significantly decreased with IL-31 and 100 ng/ml tacrolimus acting alone or in combination for 24 h. Conclusion：The expression of NT4 of keratinocyte is up-regulated by IL-31. Tacrolimus might achieve its anti-pruritus effect in atopic dermatitis by decreasing the NT4 expression of keratinocytes.