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Abstract Cancer immunotherapy is the most exciting advancement in cancer therapy. Similar to immune checkpoint blockade and chimeric antigen receptor T cell (CAR-T), bispecific antibody (BsAb) is attracting more and more attention as a novel strategy of antitumor immunotherapy. BsAb not only offers an effective linkage between therapeutics (e.g., immune effector cells, radionuclides) and targets (e.g., tumor cells) but also simultaneously blocks two different oncogenic mediators. In recent decades, a variety of BsAb formats have been generated. According to the structure of Fc domain, BsAb can be classified into two types: IgG-like format and Fc-free format. Among these formats, bispecific T cell engagers (BiTEs) and triomabs are commonly investigated. BsAb has achieved an exciting breakthrough in hematological malignancies and promising outcome in solid tumor as showed in various clinical trials. In this review, we focus on the preclinical experiments and clinical studies of epithelial cell adhesion molecule (EpCAM), human epidermal growth factor receptor (HER) family, carcinoembryonic antigen (CEA), and prostate-specific membrane antigen (PSMA) related BsAbs in solid tumors, as well as discuss the challenges and corresponding approaches in clinical application.