The present invention relates to a complex between interferon-.beta. and polyethylene glycol, which has high biological activity, and to a method for producing the complex at high efficiency. Namely, the present invention relates to a method for producing an interferon-.beta. complex comprising binding interferon-.beta. to polyethylene glycol in the presence of at least one additive selected from the group consisting of oligosaccharides having 5 or less sugar units, monosaccharides, their corresponding sugar alcohols, and C.sub.2-6 polyhydric alcohols, and to an interferon-.beta. complex produced by the method, which has polyethylene glycol specifically bound with lysine located at the 19th or 134th position in the amino acid sequence of interferon-.beta..