OBJECTIVE The purpose of this study was to investigate the molecular mechanism of LncRNA LOXL1-AS1 in non-small cell lung cancer (NSCLC). METHODS Lung cancer cell lines (H1299, A549, H520 and H596) and human normal lung epithelial cell line (BEAS-2B) were used in this study. Gene expression was measured by qRT-PCR (quantitative real-time PCR). The bioinformatics databases (miRDB and TargetScan7) were used to predict target genes. Luciferase assay and pull-down assay were processed for verifying the binding sites. CCK8 assay was used for detecting proliferation, and transwell assay was undertaken for migration and invasion. RESULTS LncRNA LOXL1-AS1 was higher expressed in lung cancer tissues and cells. Moreover, LOXL1-AS1 expression was upregulated in tumor tissues with advanced stages and metastasis. After knocking down LOXL1-AS1, proliferation, invasion and migration of H1299 and A549 cells were inhibited. Interestingly, miR-3128 was negatively regulated by LncRNA LOXL1-AS1, which inhibited the expression of RHOXF2. Rescue assay also confirmed that miR-3128 inhibitor and oeRHOXF2 could rescue the effect of down-regulated LOXL1-AS1 on proliferation, invasion and migration progression. CONCLUSIONS LOXL1-AS1 promotes the progression of NSCLC by regulating miR-3128/RHOXF2 axis, which might be a new potential target for the diagnosis and treatment of NSCLC.