The present invention provides a heterodimeric protein comprising polypeptides that bind each other containing two CH3 regions, wherein amino acid mutations are introduced into CH3 region of the first polypeptide and CH3 region of the second polypeptide to form pairs of amino acids with polar interactions on their interaction interface, thereby forming a heterodimeric protein specifically. The heterodimeric protein of the present invention can prevent Fc mismatch, avoid homodimer formation, and has high yield and good stability.