Recently, numerous studies have revealed that long non‐coding RNAs (lncRNAs) play complex roles in various lung diseases, while the colorectal neoplasia differentially expressed (CRNDE) functions in non‐small cell lung carcinomas (NSCLC) remain largely unknown. In the present study, we investigate the role and mechanism of CRNDE in the progression of NSCLC. The mRNA level of CRNDE in NSCLC patients and cells was detected by qRT‐PCR. The influence of CRNDE silencing or over‐expression on NSCLC cell proliferation and growth were assessed by MTT and flow cytometry, respectively. We also investigated the effect of abnormal CRNDE expression on cyclins and PI3K/AKT pathway. Furthermore, si‐CRNDE NSCLC cell lines were injected subcutaneously into nude mice to explore tumour formation in vivo. The expression of CRNDE was significantly upregulated in NSCLC patients and cells. In addition, both loss and gain function assays revealed that CRNDE promoted NSCLC cell proliferation and growth both in vitro and in vivo. Moreover, CRNDE regulated the cell cycle transition from G0/G1 stage to S stage and modulated the expression of CDK4, CDK6 and CCNE1. We further illustrated that CRNDE activated PI3K/AKT signalling in NSCLC cell lines. In conclusion, CRNDE was highly expressed in NSCLC malignant tissues and the heightened CRNDE strongly promoted NSCLC cell proliferation and growth through activating PI3K/AKT signalling; our results shed a light on utilizing CRNDE as a potential novel therapeutic target for the treatment of NSCLC.