This study aims to investigate the expression and significance of KPNA2 in human gastric adenocarcinoma progression and prognosis. Using immunohistochemistry and real-time reverse transcriptase polymerase chain reaction assay, we identified abnormally elevated expression of KPNA2 in gastric adenocarcinoma tissues compared to paired normal stomach mucosa tissues in 30 patients (p < 0.05). In order to investigate the correlations between KPNA2 and the clinicopathological features of gastric adenocarcinoma, the expression of KPNA2 in 142 patients with gastric adenocarcinoma was detected by immunohistochemistry, and the results showed that overexpression of KPNA2 was associated with the size of tumor (p < 0.001), histological grade (p < 0.001), lymph node involvement (p = 0.001), and tumor node metastasis stage (p < 0.001). Kaplan-Meier survival analysis showed that patients with high KPNA2 expression showed a significantly shorter overall survival time compared with patients with low KPNA2 expression. Multivariate analysis suggested that KPNA2 expression might be an independent prognostic indicator (p < 0.001) for the survival of patients with gastric adenocarcinoma. In conclusion, overexpression of KPNA2 is closely related to progression of gastric adenocarcinoma and might be regarded as an independent predictor of poor prognosis for gastric adenocarcinoma.