Abstract: Provided is a method and a device for screening an antigen epitope polypeptide. The screening method includes: predicting one or more antigen epitopes with all proteome sequences of a target coronavirus to obtain a predicted epitope region; screening a polypeptide with a differential response to a positive serum sample infected by the target coronavirus and a control serum sample with a polypeptide chip technology, and recording the polypeptide as a differential peptide fragment; comparing the differential peptide fragment with all proteome sequences of the target coronavirus to obtain a first conserved motif region; screening regions meeting epitope screening conditions from the predicted epitope region and the first conserved motif region to obtain the antigen epitope, wherein the epitope screening conditions comprise a non-phosphorylation region and/or an extracellular region of the target coronavirus.