Nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) has been recently documented in various malignancies. However, data regarding the expression and prognostic value of NUCKS in gastric adenocarcinoma are limited. Specimens from 159 gastric adenocarcinoma patients who underwent primary gastrectomy were collected. Immunohistochemical method was used to evaluate NUCKS and Ki-67 expression. The correlations between NUCKS and clinical significance were analyzed. Elevated NUCKS expression was significantly associated with TNM stage (P = 0.034), depth of invasion (P = 0.001), and expression of Ki-67 (P = 0.035). Kaplan-Meier analysis indicated that NUCKS overexpression alone (P = 0.045 for overall survival) or in combination with Ki-67 (P = 0.007 for disease-free survival, P = 0.002 for overall survival) was correlated with adverse prognosis of the patients. Multivariate analysis revealed that combined NUCKS and Ki-67 overexpression was an independent prognostic factor for both disease-free survival (hazard ratio = 1.623, P = 0.02) and overall survival (hazard ratio = 1.667, P = 0.016) in gastric adenocarcinoma patients. The combination of NUCKS and Ki-67 overexpression in gastric adenocarcinoma further distinguished a subgroup of patients with poor prognosis.