In this article, we review the current understanding of the role of IL-34 and its receptor, macrophage colony-stimulating factor-1 receptor (MCSF-1R, also termed CSF-1R or FMS), in CRC, with particular attention to the available evidence about the IL-34/MCSF-1R axis-mediated regulation of TAMs and the role of IL-34 and MCSF-1R in promoting cancer resistance to chemotherapy and immunotherapy. The gene discussed is IL34; the disease is colorectal carcinoma.