Parallels between the effects of SLFN11 and CD47 on resistance to genotoxic stress suggested that SLFN11 may be an effector mediating the selective cytoprotective effects of CD47 knockdown, prompting us to examine the regulation of SLFN11 and its orthologs by CD47 and the potential implications for combining CD47-targeted therapeutics with genotoxic cancer therapies. Here, SLFN11 is linked to cancer.