Background and Objective: Expression of Skp2 was related with the prognosis of several tumors. However, there was no intensive study on the relationship between Skp2 and extranodal NK/T-cell lymphoma. This study was to explore the role of Skp2 in extranodal NK/T-cell lymphoma. Methods: The clinicopathological data of 39 patients with extranodal NK/T-cell lymphoma were analyzed. The expression of Skp2 was examined by immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections. Results: Among the patients with high expression of Skp2, complete remission (CR) rate was only 14.3% (2/14). However, CR rate among the patients with low expression of Skp2 was 68.0% (17/25). Significant difference was shown between these two groups (P < 0.001). In the group of low expression, the median overall survival (OS) was 85.59 months (95% CI: 35.83- 135.34 months), the 1- and 2-year OS rates were 81% and 71%, respectively. However, in the group of high expression, the median OS was only 9.73 months (95% CI: 2.05-17.40 months), the 1- and 2-year OS rates were 42% and 14%, respectively. There was statistical difference between these two groups (P < 0.001). Multivariate analysis showed that Skp2 expression (P < 0.001), LDH (P = 0.026) and ECOG PS (P = 0.003) were dependent prognostic factors of extranodal NK/T-cell lymphoma. Conclusion: High expression of Skp2 is an independent unfavorite adverse prognostic factor of extranodal NK/T-cell lymphoma.