Gastric carcinoma, one of the most aggressive and lethal human malignancies, is associated with poor prognosis despite progress in therapeutic strategies. This study examined the potential function and mechanism of action of microRNA-125b-5p (miR-125b-5p) in the pathogenesis of gastric carcinoma. We recognized that miR-125b-5p was elevated in gastric carcinoma, and its decreased expression was associated with a better prognosis. Loss-of-function assays showed that miR-125b-5p suppression inhibited the proliferative and invasive abilities of gastric cancer cells. Furthermore, RING1 and YY1-binding protein (RYBP) was found to be target gene for miR-125b-5p action; miR-125b-5p negatively regulates RYBP expression.According to the results of rescue experiments, RYBP downregulation partially counteracted the miR-125b-5p silence-mediated inhibitory function in gastric cancer progression. Collectively, these data elucidated the molecular mechanisms of the miR-125b-5p/RYBP axis in gastric cancer invasion and growth.