Recent studies demonstrated that in several human malignancies aberrant expression profiles of circulating microRNAs (miRNAs) anticipate great cancer diagnostic potential. Here we showed that serum miR-378 could serve as a novel noninvasive biomarker in gastric cancer (GC) detection. Genome-wide miRNA expression profiles followed with Real-Time quantitative RT-PCR (qRT-PCR) assays revealed that miR-187^*, miR-371-5p and miR-378 were significantly elevated in GC patients. Further validation indicated that miR-378 alone could yields a ROC curve area of 0.861 with 87.5% sensitivity and 70.73% specificity in discriminating GC patients from healthy controls. Collectively, these data support our contention that serum miR-378 has strong potential as a novel noninvasive biomarker in gastric cancer detection.