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Long non-coding RNAs have been implicated in human cancer but their mechanisms of action are mainly undocumented. In this study, we found that HOXA11-AS expression was upregulated in non–small cell lung cancer tissues and cell lines. High levels of HOXA11-AS expression were correlated with larger tumor size and lymph node metastasis. Functional analysis revealed that HOXA11-AS promotes non–small cell lung cancer cell proliferation and invasion. In particular, HOXA11-AS functions as a competing endogenous RNA to regulate transcriptional factor Sp1 expression via sponging miR-124. Collectively, our findings reveal an oncogenic role for HOXA11-AS in non–small cell lung cancer tumorigenesis.