Background: This study aims to investigate the correlation of VEGF-B and FLT-1 co-expression with the prognosis of gastric cancer (GC). Materials & methods: Primary GC samples and adjacent tissues were obtained from 96 patients. Results: Both VEGF-B and FLT-1 were testified to be upregulated in the human GC compared with adjacent tissues. Spearman's rank correlation analysis indicated that VEGF-B and FLT-1 expression were correlated (r = 0.321, p = 0.0015). High VEGF-B and FLT-1 co-expression patients showed poor prognosis when compared with low VEGF-B and FLT-1 co-expression patients (p = 0.0169). Conclusion: The high co-expression of VEGF-B and FLT-1 in GC shows a poor prognosis of overall survival, and targeted therapy against the interaction between VEGF-B and FLT-1 is worth further detailed analysis.