Globally, avian influenza (AI) is a serious problem in poultry farming. Despite vaccination, its prevalence in Mexico highlights the need for new approaches to control AI and reduce the economic losses associated with its occurrence in susceptible birds. Recombinant proteins from avian influenza virus (AIV) have been expressed in different organisms such as plants. The present study was designed to investigate the feasibility of designing and expressing the hemagglutinin (HA) protein of AIV in the microalgae Chlamydomonas reinhardtii as a novel approach for AIV control and taking advantage of culture conditions, its reproduction range, and safe use in consideration of GRAS (generally regarded as safe). The knowledge and techniques of genetic modification in C. reinhardtii permit their use as an expression system and have advantages over other protein expression systems of recombinant proteins of commercial value. The results demonstrate that the HA protein of AIV in the transplastomic microalgae C. reinhardtii showed antigenic reactivity to antibodies using the Western blot test and through its application in chickens. The results of this study demonstrated antigenic activity in vitro and the in vivo of recombinant HA protein in the chloroplast of C. reinhardtii, which demonstrated its feasibility for expression in microalgae and the potential as recombinant antigen against avian influenza virus.