We constructed a novel four-gene CAF signature including SPARC, EFEMP1, RGS5 and SERPINE1 which may enhance patient stratification and prognostic prediction of GC patients.Our study provides insights into the composition of the tumor microenvironment and construction of a four-gene CAF signature associated with clinical prognosis, providing new perspectives for the clinical management of gastric cancer. Here, RGS5 is linked to gastric cancer.