Objective To investigate the effect of dexmedetomidine (Dex) on the proliferation, migration and invasion of non‑small cell lung cancer (NSCLC) by regulating the microRNA (miRNA)‑490‑3p (miR‑490‑3p)/integrin β1 (ITGB1) axis. Methods HCC‑827 cells were divided into the following groups: a control group (without treatment), a low‑dose Dex group (treatment with Dex at 25 µg/L), a medium‑dose Dex group (treatment with Dex at 50 µg/L), a high‑dose Dex group (treatment with Dex at 100 µg/L), a high‑dose Dex+inhibitor NC group (transfected with inhibitor NC followed by treatment with 100 µg/L Dex) and a high‑dose Dex+miR‑490‑3p inhibitor group (transfected with miR‑490‑3p inhibitor followed by treatment with 100 µg/L Dex), with six repeated wells in each group. The cellular optical density was measured at 490 nm by 2, 5⁃diphenyl⁃2⁃H⁃tetrazolium bromide (MTT) assay (D490). The cell proliferation rate was detected by 5‑ethynyl‑2'‑deoxyuridine (Edu) assay. The apoptotic rate was detected by flow cytometry. The cell migration and invasion were detected by Transwell chamber assay. The levels of miR‑490‑3p and ITGB1 messenger RNA (mRNA) were detected by real‑time fluorescence quantitative polymerase chain reaction (FQ‑PCR). The levels of Ki‑67 antigen (Ki‑67), matrix metalloproteinase‑9 (MMP‑9), B‑cell lymphoma‑2 (Bcl‑2), B‑cell lymphoma‑2‑associated X protein (Bax) and integrin β1 (ITGB1) were measured by Western blot. The relationship between miR‑490‑3p and ITGB1 was verified by double luciferase reporter gene experiment. A model of 20 nude mice bearing tumor was established. According to the random number table method, the mice were divided into two groups (n=10): a normal saline group (group CK) and a Dex group (group Dex). Group CK was administered with normal saline, while group Dex was given Dex at 20 µg·kg−1·d−1. Tumor mass and tumor volume were observed, and the expression of miR‑490‑3p and ITGB1 mRNA in tumor tissues was detected. The levels of Ki‑67, MMP‑9, Bax, Bcl‑2 and ITGB1 in tumor tissues were detected. Results Compared with the control group, the low‑dose Dex group, the medium‑dose Dex group, the high‑dose Dex group and the high‑dose Dex+inhibitor NC group showed increases in the HCC‑827 cell apoptotic rate, the levels of miR‑490‑3p and Bax protein, and decreases in the number of migrated and invaded cells, D490 (24 h and 48 h), the proliferation rate, and the levels of ITGB1 mRNA and Ki‑67, MMP‑9, Bcl‑2 and ITGB1 protein (all P<0.05). Compared with the low‑dose Dex group, the medium‑dose Dex group, the high‑dose Dex group and the high‑dose Dex+inhibitor NC group showed increases in the HCC‑827 cell apoptotic rate, the levels of miR‑490‑3p and Bax protein, and decreases in the number of migrated and invaded cells, D490 (24 h and 48 h), the proliferation rate, and the levels of ITGB1 mRNA and Ki‑67, MMP‑9, Bcl‑2 and ITGB1 protein (all P<0.05). Compared with the medium‑dose Dex group, the high‑dose Dex group and the high‑dose Dex+inhibitor NC group showed increases in the HCC‑827 cell apoptotic rate, the levels of miR‑490‑3p and Bax protein, and decreases in the number of migrated and invaded cells, D490 (24 h and 48 h), the proliferation rate, and the levels of ITGB1 mRNA and Ki‑67, MMP‑9, Bcl‑2 and ITGB1 protein (all P<0.05). Compared with the high‑dose Dex+inhibitor NC group, the high‑dose Dex+miR‑490‑3p inhibitor group showed decreases in the HCC‑827 cell apoptotic rate, the levels of miR‑490‑3p and Bax protein, and increases in the number of migrated and invaded cells, D490 (24 h and 48 h), the proliferation rate, and the levels of ITGB1 mRNA and Ki‑67, MMP‑9, Bcl‑2 and ITGB1 protein (all P<0.05). Compared with co‑transfection with miR‑NC and ITGB‑WT, co‑transfection with miR‑490‑3p mimic and ITGB1‑WT presented lowered luciferase activity (P<0.05). Compared with group CK, group Dex showed decreases in tumor mass, tumor volume, the levels of ITGB1 mRNA and Ki‑67, MMP‑9, Bcl‑2 and ITGB1 protein, as well as increases in the levels of miR‑490‑3p and Bax protein (all P<0.05). Conclusions Dex can inhibit the proliferation, migration and invasion of HCC‑827 cells by up‑regulating the expression of miR‑490‑3p and down‑regulating the expression of ITGB1.