Background: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor which translocates from the cytoplasm to the nucleus after activation. AhR overexpression is positively associated with epidermal growth factor (EGFR) expression in non-small cell lung cancer (NSCLC). The association between AhR expression and types of EGFR mutation, and the prognostic value of AhR expression in NSCLC remain unclear. Patients and Methods: The AhR expression and detection of L858R and E746-750A deletion of EGFR in NSCLC was assessed using immunohistochemistry. Results: Nuclear translocation of AhR was more common in females, non-smokers, adenocarcinoma (AD) and NSCLC patients with EGFR E746-750A deletion. The overall median survival time (MST) was 20.4 months for patients with NSCLC, 21.8 months for these with AD and 15.4 months for these with squamous cell carcinoma (SQ). The MST was significantly reduced in patients with poor performance status, SQ or advanced cancer stage. AhR nuclear translocation was associated with cancer death in SQ (hazard ratio=3.714, p<0.001) but not in AD (hazard ratio=0.837, p=0.407). Conclusion: Nuclear translocation of AhR was associated with EGFR mutation, and conferred a poor prognosis for patients with lung SQ.