Gastric carcinoma is one of the most common malignancies in men, and microRNA plays a critical role in regulating the signaling networks of gastric carcinoma tumorigenesis and metastasis. We first report the functional characteristics of miR-221-3p in gastric carcinoma. Quantification in gastric carcinoma cell lines and tumor samples reveals significantly increasing miR-221-3p expression. Moreover, a high level of miR-221-3p is correlated with a poor prognosis for gastric carcinoma patients. Ectopic miR-221-3p expression significantly promotes gastric carcinoma cell proliferation, invasion, and sphere formation, while silencing miR-221-3p significantly inhibits these abilities in gastric carcinoma cells. Tests in vivo showed that miR-221-3p significantly promotes tumor growth in xenograft mouse models. In this study, we reveal that miR-221-3p targets PTEN mRNA and downregulates PTEN, which is the possible mechanism of miR-221-3p-induced oncogenic properties. Collectively, we reveal a critical role for miR-221-3p in gastric carcinoma development and progression.