Purpose To investigate the association of platelet-derived growth factors (PDGFs), clinicopathological features, and prognosis in gastric cancer patients. Methods Tumor specimens of 180 individuals with gastric cancer treated between 2016 and 2020 were collected. Immunohistochemical staining and Western blot (WB) were used to detect the expression of PDGF-B and PDGF-D. The relationship between the expression of PDGF-B and PDGF-D and relapse-free subsistence (RFS) time was assessed using Kaplan–Meier curves. Univariate and multivariate Cox proportional hazards regression models were used to evaluate the relationship between the expression of PDGF-B and PDGF-D and the prognosis and clinicopathological features in gastric cancer patients. Results High expression of PDGF-B and PDGF-D was detected in 108 (60%) and 137 (76%) tumor specimens, respectively. The expressions of PDGF-B and PDGF-D were independent predictive indicators in multivariate analysis when compared to tumor depth, tumor stage, lymph node metastasis, and RFS (P < 0.01). Conclusion The high expression of PDGF-B and PDGF-D in gastric cancer tissues is associated with poor prognosis and poor survival rate of the patients. The expression of PDGF-B and PDGF-D can be used as important indicators to evaluate the biological behavior and prognosis of gastric cancer.