The invention relates to a method for preparing a homodimer protein mixture by using repulsive interaction of charges. The method comprises the step of replacing part of residues with the opposite-charged residues, so that different proteins or antibodies are unfavorable to forming heterodimers due to the repulsive interaction between like charges, while same proteins or antibodies are favorable to forming homodimers due to attractive interaction between opposite charges. The homodimer protein mixture obtained according to the method of the invention can simultaneously act on different epitopes of the same target, and simultaneously inhibit the effects of a plurality of antigens by binding to the antigens from different sources, thereby providing a new approach towards immunological diagnosis and treatment of tumors and other diseases.