Objective To investigate the regulatory effect and related mechanism of microRNA (miRNA)-4286 on sensitivity of non-small cell lung cancer cells to cisplatin. Methods The expression of miRNA-4286 in non-small cell lung cancer A549 cells and A549 cisplatin resistant cells (A549/DDP) was detected by quantitative polymerase chain reaction (qPCR). The overexpression and low expression cell models of miRNA-4286 were successfully constructed by using miRNA-4286 mimics and inhibitor, respectively, and were divided into overexpression negative control group, overexpression miRNA-4286 group, low expression negative control group, and low expression miRNA-4286 group. Cell counting kit 8 (CCK-8), plate colony-forming test and flow cytometry were used to detect the effect of miRNA-4286 expression on the sensitivity of non-small cell lung cancer cells to cisplatin. The targeting relationship between miRNA-4286 and exportin 1 (XPO1) was detected by TargetScan, qPCR, and Western blotting. Western blotting was used to detect the expression of apoptotic proteins cysteine aspartic acid specific protease 3 (caspase 3), B-cell lymphoma-related X protein (Bax) in non-small cell lung cancer cells after changing miRNA-4286 under the action of cisplatin. Results The expression of miRNA-4286 in A549 cells was significantly higher than that in A549/DDP cells (P<0.01). Under the action of 0-2 μg/mL cisplatin, the proliferation rate of A549 cells was decreased and the apoptosis rate was increased after overexpression of miRNA-4286 (P<0.05 or P<0.01); the results were opposite with low expression of miRNA-4286 (P<0.05 or P<0.01). The mRNA and protein expression levels of XPO1 in A549 cells were decreased after overexpression of miRNA-4286 (P<0.05 or P<0.01), the results were opposite with low expression of miRNA-4286 (P<0.05 or P<0.01). Under the action of cisplatin, down-regulation of miRNA-4286 inhibited the expression of apoptotic proteins caspase 3 and Bax in A549 cells, and down-regulation of XPO1 could negatively regulate this effect (P<0.05 or P<0.01). Conclusion miRNA-4286 can target XPO1 and regulate the sensitivity of non-small cell lung cancer A549 cells to cisplatin, and the mechanism may be related to the apoptosis pathway.