In the end of twentieth century antibodies with uncommon structure were detected in mammals of Camelidae family (which include camels, llamas, alpacas) along with traditional type of IgG antibodies. These antibodies were designated VHH (variable heavy-heavy) and have an antigen-binding pocket containing heavy chain variable region and lacking light chain. Recombinant VHH-antibodies have several advantages over single-chain antibodies derived from conventional molecules of IgG such as simplicity of genetic manipulation, high expression in different systems, good solubility, high stability in a wide range of conditions and better tissue penetration due to smaller size (15-30 kDa). Structural properties of VHH-antibodies facilitate in construction of immune phage libraries, which has great potential for precise engineering of antibodies specific to target proteins. Variable domains of VHH-antibodies may be used in particular as a framework for design of synthetic libraries since only three CDR-fragments of VHH-antibody are required for high affinity binding. It is known that CD47 protein is expressed at high level on the surface of many cancer cells. CD47 interacts with SIRPa receptor, which is present on macrophages resulting in phagocytosis inhibition. Thus cancer cells can escape their recognition by the host immune system. CD47-SIRPa interaction is considered as a promising target for cancer therapy. One approach comprises of using of monoclonal antibodies which block CD47 protein allowing macrophages to engulf cancer cells. However, antibodies with properties suitable for clinical application are still under development. Our aim is to develop a new high affinity anti-CD47 VHH-antibody, which has a better blocking action, smaller size and minimal toxicity. To achieve this goal we immunized alpacas with extracellular fragment of human CD47 protein, isolated mRNA from PBMCs and generated PCR-fragments with VHH sequences to obtain VHH library. Further we performed selection of specific antibodies using phage display technology. Now we are studying the characteristics and functional activity of such VHH-antibodies. We suggest that these new anti-CD47 VHH-antibodies might prove perspective and suitable for cancer therapy.