The replication protein A (RPA)1-4 family are single-stranded DNA-binding proteins that are essential components of DNA replication, repair and recombination, and cell cycle regulation. The present study aimed to evaluate the prognostic value of the RPA family members in patients with gastric cancer (GC), using datasets retrieved from the Oncomine public database. Datasets were retrieved for the purpose of comparing the RPA expression levels between GC and normal tissues. Additionally, Kaplan-Meier analysis was used to compare the overall survival (OS) times of GC patients that expressed different levels of RPA proteins. RPA1, 2, and 3 expression levels were all significantly upregulated in gastric intestinal-type, diffuse gastric, and gastric mixed adenocarcinomas, compared with those in normal mucosal tissues. Moreover, high mRNA expression levels of RPA3 and 4 predicted poorer OS times in all GCs, as well as patients with human epidermal growth factor receptor 2-negative and -positive GC. The high-risk group, separated by RPA signature, showed a poorer outcome than the low-risk group. RPA3 was the most strongly correlated with CD4+ T-cell levels. In conclusion, RPAs are novel prognostic indicators in GC, and can also predict the features of immunological diseases. Future experimental investigation into the roles of RPAs concerning the pathogenesis and development of GC may provide a novel biomarker or therapeutic target, improving the prognosis of patients with GC.