Objective. To investigate the correlation of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its specific receptor fibroblast growth factor-inducible immediate-early response protein 14 (Fn14) to cervical carcinogenesis by examining TWEAK/Fn14 expression levels or locations in different cervical tissues and cells. Methods. TWEAK/Fn14 mRNA expressions were detected by quantitative real-time PCR in total of 120 cervical samples including normal, precancerous and cancerous tissues, while protein expressions were detected by immunofluorescent staining and western blot in both tissues and cell lines. Correlation between TWEAK expression levels to cancer progression and clinicopathologic features was statistically analyzed. Results. The TWEAK expression was significantly decreased while Fn14 expression was increased in carcinoma and cervical intraepithelial neoplasm (CIN) specimens compared with that in normal control specimens. A similar trend of TWEAK/Fn14 expression was also observed in cervical cell lines. In addition, TWEAK expression decreased further along with the interstitial depth of invasion (P<0.05) and tumor grade (P<0.05), suggesting that TWEAK acts rather on local cancer tissue infiltration. Conclusion. TWEAK/Fn14 pathway may play a role in the development of squamous cervical carcinoma, in which the reduced level of TWEAK could promote the progression and invasion of cervical cancer. An increase in Fn14 may reflect a compensatory response to decreased TWEAK and may provide a novel therapeutic target for human cervical cancer treatment or a biomarker for cervical cancer diagnosis. (C) 2011 Elsevier Inc. All rights reserved.