Background: Gastric cancer (GC) as one of the most common cancers, serves as the third cause of cancer-related death. Insulin-like growth factor binding protein 3 (IGFBP-3) and its novel death receptor (IGFBP-3R) has been shown to have an anti-tumor effect however their prognostic values have not been elucidated yet. Methods: IGFBP-3 and IGFBP-3R expression were evaluated with quantitative real-time polymerase chain reaction and western blotting in patients with GC (N=68). The relationship between prognostic factors such as tumor stage, tumor grade, tumor size, metastases, and Overall Survival (OS) with IGFBP-3/IGFBP-3R expression was also assessed. Results: IGFBP-3 and its death receptor expression were determined as dialectic evidence. In the experimental procedure, IGFBP-3 and IGFBP-3R expression were reduced in tumor tissues significantly. We found that there was an association between the reduction of IGFBP-3 with lymph node metastasis and TMN staging ( P<0.001 ). In addition, IGFBP-3R expression was associated with tumor size ( P=0.004 ), lymph node metastasis ( P<0.001 ), differentiation ( P=0.002 ) and TNM classification ( P=0.005 ). Interestingly, we presented that the downregulation of IGFBP-3R was stage-dependent. In OS analysis, we offered that low levels of IGFBP-3R mRNA expression were unfavorable with survival rate (P=0.002 ). IGFBP-3 regardless of its relationship with some prognostic parameters, there was no significant relationship between IGFBP-3 and OS. Conclusion: The findings of this study showed that IGFBP-3R has the potential to be a new prognostic biomarker of GC. But despite some benefit of IGFBP-3, it cannot be accepted as a prognostic biomarker. However, this finding must be improved and confirmed by future studies.