Overexpression of Smad4 exerted no influence on P‐Smad2 and P‐Smad3 expression, but significantly increased Smad4 and Foxp3 expression, ZIKV infection still significantly reduced P‐Smad2, P‐Smad3, Smad4 and Foxp3 expression. Here, SMAD4 is linked to Zika virus infectious disease.