The *MYC* oncogene, which is overexpressed in many human cancers, regulates the expression of two immune checkpoint proteins, CD47 and PD-L1, on the surface of tumor cells. Suppression of *MYC* in mouse tumors and human tumor cells reduces the levels of CD47 and PD-L1 mRNA and protein. MYC binds directly to the promoters of these genes. Inactivated *MYC* in mouse tumors downregulates CD47 and PD-L1 expression, enhancing the anti-tumor immune response. Conversely, enforced expression of CD47 or PD-L1 in tumors suppresses the immune response and allows tumors to grow. This suggests that MYC initiates and maintains tumorigenesis by modulating immune regulatory molecules. MYC's regulation of CD47 and PD-L1 may be a general mechanism for tumor cells to evade immune surveillance. Therapeutic strategies targeting MYC could potentially restore the immune response against cancers, particularly those with high MYC expression.The *MYC* oncogene, which is overexpressed in many human cancers, regulates the expression of two immune checkpoint proteins, CD47 and PD-L1, on the surface of tumor cells. Suppression of *MYC* in mouse tumors and human tumor cells reduces the levels of CD47 and PD-L1 mRNA and protein. MYC binds directly to the promoters of these genes. Inactivated *MYC* in mouse tumors downregulates CD47 and PD-L1 expression, enhancing the anti-tumor immune response. Conversely, enforced expression of CD47 or PD-L1 in tumors suppresses the immune response and allows tumors to grow. This suggests that MYC initiates and maintains tumorigenesis by modulating immune regulatory molecules. MYC's regulation of CD47 and PD-L1 may be a general mechanism for tumor cells to evade immune surveillance. Therapeutic strategies targeting MYC could potentially restore the immune response against cancers, particularly those with high MYC expression.