Provided is modified interferon (IFN)-beta polypeptide comprising a specified amino acid sequence or its variant modified by the presence of one or more non-naturally encoded amino acids therein, each non-naturally encoded amino acid being present at a residue position selected from 36 and 111 or corresponding residue position(s), wherein the non-naturally encoded amino acid is p-acetyl-phenylalanine (pAF), and wherein said IFN beta polypeptide is linked to a water-soluble polymer comprising a poly(ethylene glycol) moiety and having a molecular weight of about 30 kDa or about 40 kDa. Further provided are corresponding DNA sequences and use of the compositions for manufacturing medicaments for cancer and viral infections.