Introduction <p>DNA damage-inducible transcript 4 (DDIT4), also known as Redd1, Dig2, and RTP801 was identified to be upregulated in response to a variety of cellular stresses, including DNA damage, endoplasmic reticulum stress, and energy stress. Several studies have discovered that dysregulation of DDIT4 involved in various cancers with paradoxical expression and roles. Hence, this study was designed to investigate the clinical significance and prognostic value of DDIT4 in different subtypes of gastric cancer (GC).</p> Materials and methods <p>To evaluate the expression pattern of DDIT4 in GC tissues as well as adjacent normal tissue, we utilized immunohistochemistry on tissue microarray (TMA) slides.</p> Results <p>Our findings revealed that nuclear expression of DDIT4 was higher in GC tissues than in non-malignant samples. Also, the cytoplasmic and membranous expression of DDIT4 were significantly lower in tumor samples (<i>P</i> = <i>0.007</i> and <i>P</i> = <i>0.002</i>, respectively). The results indicated that there was a statistically significant association between low cytoplasmic and membranous expression of DDIT4 and advanced histological grade (<i>P</i> = <i>0.001</i> and <i>P</i> = <i>0.016</i>). The survival analysis revealed that lowered cytoplasmic expression of DDIT4 is significantly associated with worse DSS (<i>P</i> = <i>0.038</i>).</p> Conclusion <p>Lower cytoplasmic expression of DDIT4 could serve as a promising prognostic biomarker in GC.</p>