Abstract： Objective： To observe the gene expression of HOX transcript antisense RNA(HOTAIR) in serum and in tissues，the distribution of Chinese medicine syndromes，therapeutic effect，and their internal relationship in patients with advanced non-small cell lung cancer(NSCLC) who were treated by epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR- TKIs) and were resistant to the drug； and to provide the basis of Chinese medicine syndrome differentiation for NSCLC patients after targeted therapy. Methods：A total of 89 patients with advanced NSCLC diagnosed by histophiology from March 2017 to April 2019 were selected for EGFR- TKIs treatment and were differentiated according to the Chinese medicine syndrome types. Tumor tissues and serological specimens were collected before and after treatment；the HOTAIR levels in them were detected before and after EGFR-TKIs treatment and after drug resistance；the relationship between the EGFR-TKIs treatment and HOTAIR gene expression and distribution of Chinese medicine syndrome was analyzed. Results： After two months of EGFR-TKIs treatment，the relative expression of HOTAIR in tumor tissues and serum of NSCLC patients was lower than that before treatment，differences being significant(P＜0.05). The relative expression of HOTAIR in tumor tissues and serum of patients with EGFR- TKIs resistance was higher than that of patients without EGFR- TKIs resistance， differences being significant(P＜0.05). The Chinese medicine syndromes of patients with EGFR-TKIs resistance were mainly yin deficiency and blood stasis syndrome and dual deficiency of qi and qi syndrome；the Chinese medicine syndromes of patients without EGFR- TKIs resistance were mainly qi deficiency and blood stasis syndrome and qi deficiency and phlegm dampness syndrome，the difference being significant(P＜0.05). Conclusion：Both EGFR-TKIs treatment and drug resistance for NSCLC patients are related to the gene expression of HOTAIR， and EGFR- TKIs treatment has an impact on the distribution of Chinese medicine syndromes in NSCLC patients.