Despite great advances in the treatment of oncological diseases, the development of medical technologies to prevent or reduce complications of therapy, in particular, those associated with surgery and the introduction of antibiotics, remains relevant. The aim of the study was to evaluate the effectiveness of the use of autoprobiotics based on indigenous non-pathogenic strains of Enterococcus faecium and E. hirae in the complex therapy of colorectal cancer (CRC) in the early postoperative period. The use of autoprobiotics did not cause side effects and led to a decrease in the level of pro-inflammatory cytokines (IL-6 and IL-18) in the blood serum. The features of the intestinal microbiome in patients with CRC were revealed, which are fundamentally different from those of other authors by an increase in alpha- biodiversity, lactobacilli, bifidobacteria, Bacteroides thetaiotaomicron and its additional differences associated with the absence of non-pathogenic enterococci: a greater amount of Parvimonas micra, a smaller amount of Akkermansia spp., an increase in the content of Klebsiella sp., Fusobacterium nucleatum and Clostridium perfringens. The use of autoprobiotics led to the elimination of P. micra, a decrease in C. perfringens, which led to the normalization of the microbiota in most patients. The effectiveness of autoprobiotics in the treatment of CRC has been proven, which, apparently, is associated with a change in the composition of intestinal microbiocenosis.