Abstract： Objective To study the signal transduction mechanism of nicotine induced periodontal ligament fibroblasts (PDLFs) apoptosis. Methods This study used 1 μg/ml, 10μg/ml and 100μg/ml nicotine to intervene PDLFs cells for 24h separately. NF-κB, p53, I-κB and Caspase3 expression were detected. Results After Nicotine was done on PDLFs cells for 24h, the transcription of p53, and Caspase3,and the translation of Caspase 3 protein were increased, while NF-κB was decreased. At the same time, the transcription of NF-κB decreased gradually with the concentration of nicotine increased ( r = 0. 707, F =33. 705, P ＜0. 01 ), nevertheless, I-κB was reversed ( r =0. 964, F =374. 883, P ＜0. 01 ). p53 expression was increased gradually with the concentration of nicotine increased ( r =0. 957, F = 153. 377, P ＜0. 01).Both Caspase3 mRNA (r =0.935, F =318.371, P ＜0.01) and protein (r =0.677, F =8. 459, P ＜ 0. 05 )increased gradually. Conclusion Nicotine induced PDLFs apoptosis was mediated through NF-κB and p53 pathway.