Nucleobindin 2 (NUCB2) has been demonstrated to play critical roles in tumorigenesis and tumor development of breast cancer. The expression change of nucleobindin 2 at mRNA level in prostate cancer (PCa) tissues compared with adjacent benign prostate tissues was detected by using real-time quantitative reverse transcriptase-polymerase chain reaction analysis in our previous study. The data suggests that NUCB2 is a cancer-related gene associated with the aggressive progression and biochemical recurrence-free survival predictor of PCa patients. However, the correlation between the expression of the NUCB2 mRNA and the overall survival of patients with PCa was not analyzed. Thus, the association of NUCB2 mRNA expression with overall survival of PCa patients was analyzed in this study. Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the correlation between NUCB2 mRNA expression and prognosis of PCa patients. The Kaplan-Meier survival analysis showed that the high expression of NUCB2 was related to the poor overall survival of patients with PCa. Multivariate Cox analysis showed that NUCB2 mRNA was an independent prognostic factor for overall survival of patients with PCa. In conclusion, we demonstrated that high NUCB2 mRNA expression correlated with poor overall survival in patients with PCa.