Abstract: Objective: To explore the influence and clinical significance of cyclindependent kinase inhibitor 2A (CDKN2A) inactivation on small cell lung cancer(SCLC) . Methods: The gene and protein expression of CDKN2A in SCLC tissue of 72 cases and non-tumor lung tissue of 68 cases were detected by the semi-quantitative RT-PCR, IHC and Western blot. Results: The CDKN2A and its first and second exon mRNA expression of SCLC were significantly less than that of non-tumor lung tissue,and there was statistical significance between their diffenence(P ＜ 0. 01) . The protein expression rate of CDKN2A in SCLC(68. 1%) was significantly higher than that of non-tumor lung tissue(36. 8%) (P ＜ 0. 01) . The protein expression of CDKN2A in SCLC was significantly lower than that of non-tumor lung tissue(P ＜ 0. 05) . There was not statistical significance between the CDKN2A expression in different pathological stages and lymph node metastasis of SCLC tissue (P ＞ 0. 05) . Conclusions: The CDKN2A gene mutation and its encoded protein inactivation are related to the development and progression of SCLC.