MicroRNAs (miRNAs) are a type of small noncoding RNAs that are strongly implicated in carcinogenesis. However, the potential diagnostic, prognostic and therapeutic roles of the majority of miRNAs in the pathological processes of tumorigenesis remain largely unknown. Our and others' data revealed that miR-204-5p was significantly downregulated in gastrointestinal tumor tissues compared with adjacent noncancerous tissues. The downregulation of miR-204-5p was confirmed in our gastric cancer (GC) cohort, and we showed that ectopic expression of miR-204-5p inhibited, whereas silencing miR-204-5p expression promoted GC cell proliferation in vitro. Subsequent mechanistic investigations identified that USP47 and RAB22A are direct functional targets of miR-204-5p in GC. Silencing the expression of USP47 and RAB22A using siRNA phenocopied the proliferation-inhibiting function of miR-204-5p in GC cells. Our results uncovered that miR-204-5p acts as a tumor suppressor in GC through inhibiting USP47 and RAB22A.