Human esophageal cancer related gene-4 （ECRG4， also known as C2ORF40） is a special tumor suppressor gene. Bioinformatics analysis has shown that the ECRG4 gene is highly conserved among different species， and has a wide distribution in the body tissues， suggesting its diverse physiological functions. Recent studies have shown that the ECRG4 gene encodes a hormone-like propeptide （Ecrg4）， which not only suppresses tumors， but also participates in the regulation of various physiological and pathological processes including inflammatory response. However， the specific mechanism of Ecrg4 in regulating inflammatory response is not well defined. This article summarized the discovery， distribution， expression characteristics， and tumor-suppressing effects of ECRG4， and discussed the role of Ecrg4 in natural immunity and inflammatory response.