The invention belongs to the field of biological medicines and relates to a composite interferon cysteine mutant and a polyethylene glycol derivative thereof, a preparation method and a medicinal composition of the polyethylene glycol derivative and an application of the two in preparing a medicine for treating viral diseases. The composite interferon cysteine mutant is obtained by mutating the amino acid on the 77th site from the N-terminal in the amino acid sequence of the composite interferon into cysteine; and the polyethylene glycol derivative of the composite interferon cysteine mutant is obtained by connecting the composite interferon cysteine mutant with a polyethylene glycol modifier, wherein the molecular weight of the polyethylene glycol modifier is 5-40KDa. The composite interferon cysteine mutant and the polyethylene glycol derivative thereof provided by the invention have high bioactivity, good pharmacological action and stability and reliable safety.