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Objective To investigate the expression changes of histone deacetylase 7（HDAC7） and ubiquitin-specific peptidase 10（USP10） in non-small-cell lung cancer （NSCLC） tissues and their significance. Methods Ninety-eight NSCLC patients underwent tumor resection, with cancer tissues and adjacent tissues preserved during the operation. Immunohistochemistry was used to detect the expression of HDAC7 and USP10 in tissues. Spearman correlation analysis was used to analyze the correlation between HDAC7 and USP10 expression in NSCLC cancer tissues, and to analyze the relationships between HDAC7 and USP10 expression and the clinicopathological parameters of NSCLC patients. Kaplan-Meier survival curve was used to analyze the relationship between HDAC7 and USP10 expression and the prognosis of NSCLC patients, and the COX multivariate proportional hazard model was used to analyze the factors for the prognosis of NSCLC patients. Results The positive rates of HDAC7 in the NSCLC tissues and adjacent tissues were 65. 31% （64/98） and 6. 12% （6/98), respectively （χ2 =74. 756, P<0. 05). The positive rates of USP10 in the NSCLC tissues and adjacent tissues were 63. 27% （62/98） and 8. 16% （8/98), respectively （χ2 =64. 800, P<0. 05). The positive expression rates of HDAC7 and USP10 in cancer tissues with stage III NSCLC, low tumor differentiation, and lymph node metastasis were higher than those with TNM stage Ⅰ–Ⅱ, high and medium differentiation, and no lymph node metastasis （all P<0. 05). The expression of HDAC7 and USP10 in NSCLC cancer tissues showed a significant positive correlation （r=0. 714, P<0. 05). The 3-year cumulative survival rates of HDAC7 positive and USP10 positive patients were lower in comparison with those of HDAC7 negative and USP10 negative patients （ χ2 =16. 300, 15. 870, respectively； all P<0. 05). Positive HDAC7 expression, positive USP10 expression, poorly differentiated tumor, lymph node metastasis, and TNM stage III were independent risk factors for the prognosis of NSCLC patients. Conclusion HDAC7 and USP10 are highly expressed in NSCLC tissues, HDAC7 and USP10 may synergistically promote the development and progression of NSCLC, and the prognosis of NSCLC patients with high expression levels of HDAC7 and USP10 is poor. [ABSTRACT FROM AUTHOR]