Cancer continues to be one of the leading causes of death worldwide. Due to genome instability, solid tumors are characterized by high heterogeneity of tumor-associated antigen expression, which makes a great challenge for targeted tumor therapy. Targeting two molecular receptors overexpressed on tumor cells is a way to overcome this problem and improve therapeutic efficacy. In this study we used truncated ferritin L-subunit (FTLsh, lacking 34 a.a. at the carboxyl terminus) as a scaffold for creating a hybrid protein for simultaneous targeting on human epidermal growth factor receptor 2 (HER2) and epithelial cell adhesion molecule (EpCAM), both of which are frequently overexpressed in epithelial carcinomas. As HER2/EpCAM-specific binders we use proteins of non-IgG nature based on ankyrin repeats (Designed Ankyrin Repeat Proteins) - DARPin_9-29 and DARPin-EC1. The hybrid protein DARP_9-29-FTLsh-EC1 generated by genetic method was conjugated to monomethyl auristatin E (MMAE). The protein-drug conjugate DARP_9-29-FTLsh-EC1/MMAE was shown to be mainly composed of dimeric form. The receptor-specific binding and internalization properties of DARP_9-29-FTLsh-EC1 fusion protein were confirmed by flow cytometry and confocal microscopy. In vitro cytotoxicity was shown to be HER2/EpCAM specific and strongly correlated to receptor density. In vivo studies have shown that DARP_9-29-FTLsh-EC1/MMAE is selectively accumulated in HER2/EpCAM-positive tumors in a mouse xenograft model causing significant tumor reduction. Our results demonstrate that bispecific targeting opens new prospects for the development of precise anticancer therapy.