Objective To investigate the relationships of 14-3-3zeta protein expression with the therapeutic efficacy and prognosis of the patients with mantle cell lymphoma (MCL). Methods Clinical data of 12 MCL patients who were confirmed pathologically and treated in the Department of Hematology of Xijing Hospital between March 2007 and March 2012 were collected and analyzed. The protein expression of 14-3-3zeta in the patients was detected immunohistochemically, and its correlation with the prognosis of the patients was analyzed. Results Compared with reactive lymphoid hyperplasia, 8 cases showed positive expression of 14-3-3zeta in the cytoplasm, accounting for 66.7%. The overall response rate (ORR), and 2-year overall survival (OS) and 2-year progression-free survival (PFS) were 62.5%,50.0% and 37.5% respectively in the patients with positive expression of 14-3-3zeta, significantly lower than those in the negative expression patients (75.0%, 100.0 and 75.0%). Our results need in-depth study with larger samples. Conclusion MCL patients have abnormally high expression of 14-3-3zeta protein, and its expression level may be correlated with the patients’prognosis.