Background: The role of plasma heat shock protein 90alpha (Hsp90 alpha) in gastric cancers remains unclear. This study aimed to clarify the diagnostic and prognostic value of plasma Hsp90 alpha in gastric cancer. Methods: Data regarding 976 gastric cancer, 50 gastric inflammatory diseases, and 100 healthy controls were collected. Plasma Hsp90 alpha levels in gastric cancer were compared to those in controls. Its correlation with tumor biomarkers and immune cells was examined. The association of plasma Hsp90 alpha with clinical features and the diagnostic and prognostic value in gastric cancer were also determined. Results: Plasma Hsp90 alpha levels were remarkably increased in gastric cancer, compared to those in gastric inflammatory diseases and healthy controls. Moreover, plasma Hsp90 alpha was correlated with CEA, CA125, CA153, CA199, T cells, Th/Ts ratio, and B cells. Plasma Hsp90 alpha was also associated with the metastasis stage. Multivariate logistic regression analysis revealed that Hsp90 alpha, B cells, and T cells were significantly associated with gastric cancer. Plasma Hsp90 alpha has a moderate diagnostic value, which increased when combined with B cell, T cells. Finally, plasma Hsp90 alpha was not associated with the survival of gastric cancer patients. Conclusion: Plasma Hsp90 alpha was elevated in gastric cancer and correlated with tumor biomarkers and immune cells. Plasma Hsp90 alpha was associated with the metastasis stage and had moderate diagnostic performance but little prognostic value in gastric cancer.