AKR1C1 is a member of the AKR1C family, which not only plays an important role in hormone metabolism but is believed to be involved in carcinogen metabolism. Our previous study demonstrated that AKR1C1 was highly expressed in lung tumor tissues as compared with the tumor-adjacent tissues. Small-cell lung cancer (SCLC) is a special type of lung cancer. Surgical treatment of SCLC is usually difficult due to the high degree of malignancy and early metastasis, and difficulty in obtaining clinical specimens. There is not much basic or clinical research on SCLC in the People’s Republic of China even in recent years. To investigate the mechanism of AKR1C1 in the pathogenesis of SCLC, the present study used H446 cell line to see whether AKR1C1 could affect the proliferation or migration of SCLC cells, and used a lentivirus to build the AKR1C1 overexpression and under-expression cell lines. The results indicated that AKR1C1 was an important inducement in the proliferation and migration of H446 cells. AKR1C1 promoted cell proliferation and played a vital role in the migration of SCLC cells. These results were also verified in nude mice in vivo. In conclusion, AKR1C1 plays an important role in the development and progression of SCLC and may represent an independent biomarker for assessment of the primary prognosis and therapy of SCLC.