BACKGROUND The lncRNA Colorectal Neoplasia Differentially Expressed (CRNDE) gene has been reported as a potential oncogene in NSCLC. Nevertheless, the molecular mechanism of CRNDE in NSCLC progression remains largely unknown. MATERIAL AND METHODS qRT-PCR assay was performed to detect the expression levels of CRNDE, miR-641, and cyclin-dependent kinase 6 (CDK6) in NSCLC. Western blot assay was employed to assess CDK6 protein level in treated NSCLC cells. si-CRNDE#1, si-CRNDE#2, miR-641 mimics, miR-641 inhibitors, or Vector-CDK6 were transfected into NSCLC cells to change the expression levels of CRNDE, miR-641, or CDK6. Dual-luciferase reporter assay was performed to validate the direct interrelated miRNA of CRNDE and the potential target of miR-641. MTT and flow cytometry assays were performed to assess the capacities of cell proliferation and apoptosis, respectively. RESULTS CRNDE level was upregulated in NSCLC, and its knockdown suppressed NSCLC cells proliferation and enhanced apoptosis, whereas miR-641 antagonized the regulatory effect of CRNDE knockdown by directly binding to CRNDE. Moreover, CDK6 was a target of miR-641 and miR-641 exerted anti-proliferation and pro-apoptosis effects through CDK6. CONCLUSIONS CRNDE promoted proliferation and inhibited apoptosis of NSCLC cells at least in part by regulating the miR-641/CDK6 axis, suggesting that CRNDE is a potential therapeutic target for NSCLC treatment.