Chemoresistance is one of the most important biological elements affecting the progression and prognosis of cancer. Long non-coding RNAs (lncRNAs) are important regulators and are aberrantly expressed in various types of cancer in humans, including non-small cell lung cancer (NSCLC). The present study aimed to investigate the effect of lncRNAs on NSCLC resistance to chemotherapy. The relative expression level of epidermal growth factor receptor antisense RNA 1 (EGFR-AS1) was quantified by reverse transcription-quantitative polymerase chain reaction analysis in NSCLC tissues, paired adjacent normal tissues, patient plasma and NSCLC cell lines, and its association with prognosis was assessed by multivariate analysis. The biological functions of EGFR-AS1 in NSCLC cells were determined in vitro. It was found that EGFR-AS1 was abnormally upregulated in NSCLC tissues compared with adjacent normal lung tissues. Furthermore, patients with NSCLC with increased expression of EGFR-AS1 had a poor prognosis. EGFR-AS1 knockdown significantly inhibited NSCLC malignancy in vitro, including cell proliferation and chemoresistance. Furthermore, the expression levels of EGFR-AS1 were increased in plasma samples from patients with cisplatin-based chemotherapy resistance. Bioinformatics analysis and a luciferase reporter assay confirmed that EGFR-AS1 mediated cell proliferation and chemoresistance through directly binding to microRNA-223. Therefore, EGFR-AS1 overexpression-induced chemoresistance can contribute to poor prognosis in NSCLC.Abbreviations: lncRNA, long non-coding RNA; NSCLC, non-small cell lung cancer; EGFR-AS1, epidermal growth factor receptor antisense RNA 1; PRC2, proteasome component 2; LSD1, lysine demethylase 1A; DNMT1, DNA methyltransferase 1; RT-qPCR, reverse transcription-quantitative polymerase chain reaction; ceRNA, competitive endogenous RNA; IGF1R, insulin-like growth factor 1 receptor; PI3K, phosphatidylinositol 3-kinase

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