Abstract: Objective To investigate the expression of C3 subtype of aldosterone reductase family 1 （AKR1C3） in non-small cell lung cancer （NSCLC） and its clinical significance. Methods Eighty-eight cases of surgically resected NSCLC tissues and 83 cases of paraneoplastic normal tissues were collected from January 2013 to March 2016. The expression of AKR1C3 in the tissues were detected by real-time quantitative PCR （QPCR）， and the expression of AKR1C3 in NSCLC tissues and adjacent normal tissues were compared. The relationship between the expression of AKR1C3 in NSCLC tissue and the clinicopathological parameters of NSCLC （sex， age， TNM stage， tumor size， histological type， lymph node metastasis） was analyzed. Based on the follow-up data， the relationship between the AKR1C3 and the prognosis was analyzed. The receiver operating characteristic curve （ROC） was used to evaluate the effectiveness of AKR1C3 in the early diagnosis of NSCLC. Results The expression of AKR1C3 in the NSCLC group was （0.187±0.175）， lower than that in the adjacent normal tissues （1.079 ±0.384）， and the difference was statistically significant （P＜0.05）. The area under the NSCLC curve of tissue AKR1C3 was 0.982 （95％CI： 0.966-0.998）. The expression of AKR1C3 in NSCLC tissue were independent of sex， age， histological type and lymph node metastasis， but related with tumor size and TNM staging. The expression of AKR1C3 in tissue more than 3 cm was （0.095±0.055）， lower than （0.340±0.201） in tissue less than 3 cm （P＜0.05）. The expression of AKR1C3 in tissue of Ⅲ and Ⅳ was （0.094±0.058）， lower than （0.265±0.202） in tissue of Ⅰ and Ⅱ stage. The median OS of the whole group was 17.60 months. The median OS of the patients with AKR1C3 high level was 20.60 months， higher than that of the lower level 11.90 months， and the difference was statistically significant （P＜0.05）. Conclusion The expression of AKR1C3 in NSCLC tissue is decreased， and it is related to TNM stage， tumor size and prognosis. It may be related to the occurrence and development of NSCLC， and is valuable in NSCLC diagnosis and disease evaluation.