Cold-inducible RNA-binding protein (CIRBP) is recently reported to be an important protective cellular molecule, and under the conditions such as hypothermia, ischemia and hypoxia, and ultraviolet radiation, the protein binds to various specific target molecules and participates in DNA damage repairing, post-transcriptional regulation, and protein translation, and thus plays a crucial regulatory role in cellular stress response. Since CIRBP is closely related to the regulation of cell proliferation, apoptosis, differentiation, rhythms and inflammation, it exerts significant effects on tumor, nervous system diseases, cardiovascular and cerebrovascular diseases and inflammation-related diseases. We mainly summarize and review the roles of CIRBP in common chronic diseases and associated mechanisms.