BACKGROUND: PIWI-like protein 1 (PIWIL1) is an important member of the Argonaute protein family and is closely related to the malignant behaviors of tumor cells. This study aimed to investigate the relationship between PIWIL1 and gastric cancer (GC). METHODS: We investigated PIWIL1 expression status in GC tissues as well as its association with clinicopathological characteristics and prognosis of GC patients. PIWIL1 siRNA was transfected into a GC cell line to elucidate its impact on malignant biological behavior. RESULTS: The results showed that PIWIL1 was upregulated in GC tissues and correlated with tumor differentiation, lymph node status, and TNM stage. The high PIWIL1 expression was an independent predictor for the prognosis of patients with GC. Silencing of PIWIL1 expression in GC cell lines suppressed tumor cell proliferation, migration, and invasion. CONCLUSION: High PIWIL1 expression suggests a poor prognosis for GC patients and PIWIL1 can serve as an important molecular marker for predicting the prognosis of GC patients.