ABSTRACT Gastric cancer (GC) is one of the most common and lethal cancers worldwide. The Nudix hydroxylase (NUDT) genes have been reported to play notable roles in tumor progression. However, the role of NUDT10 in GC has not been reported. In this study, we investigated the expression of NUDT10 in GC and its association with clinicopathological characteristics. Quantitative real-time polymerase chain reaction and analyses of The Cancer Genome Atlas and Human Protein Atlas databases were performed to determine NUDT10 mRNA and protein expression. Receiver operating characteristic curve analysis was used to assess the diagnostic value of NUDT10 in patients with GC. We used Cox regression and the Kaplan–Meier method to assess the correlations between clinicopathological factors and survival outcomes of patients with GC. Gene set enrichment analysis (GSEA) was performed to identify the underlying signaling pathways. NUDT10 mRNA and protein expression was significantly lower in GC tissues compared to normal tissues. Interestingly, higher NUDT10 expression was correlated with advanced tumor stage, deeper local invasion, and worse survival outcomes. Patients with higher NUDT10 expression had a significantly worse prognosis than those with lower NUDT10 expression. Multivariate analysis showed that high NUDT10 expression was an independent predictor of survival outcome. Several pathways, including mismatch repair, nucleotide excision repair, extracellular matrix receptor interaction, and cancer signaling, were identified as enriched pathways in GC through GSEA. To our knowledge, this study is the first to characterize NUDT10 expression in GC. Our study demonstrates that NUDT10 is a promising independent biomarker for GC prognosis.