Objective To explore the effect of zerumbone on proliferation, migration and invasion of non-small cell lung cancer cell line and underline mechanism. Methods Human non-small cell lung cancer cells line A549 was divided into control group, zingerone-low dose group, zingerone-medium dose group, zingerone-high dose group, pcDNA group, pcDNA-FBXW7 group, and zingerone-high dose group +si-NC group, zingerone-high dose +si-FBXW7 group. Cell proliferation inhibition was detected by methyl thiazolyl tetrazolium (MTT) method, cell migration and invasion were detected by Transwell assays, and the expression of F-box with 7 tandem WD40 (FBXW7) mRNA and protein were detected by Western blot and real-time(RT-qPCR). Results Compared with control group, the proliferation, migration and invasion of A549 cells in the zingerone-low, medium and high dose groups were significantly reduced (P＜0.05), the expression of FBXW7 mRNA and protein were significantly increased (P＜0.05). Compared with the pcDNA group, the proliferation, migration and invasion of A549 cells in the pcDNA-FBXW7 group were significantly reduced (P＜0.05). Compared with the Zingerone-high-dose+si-NC group, the cell proliferation, migration and invasion ability of A549 in the Zingerone-high-dose+si-FBXW7 group was significantly increased (P＜0.05). Conclusions Zerumbone reduces proliferation, migration and invasion of non-small cell lung cancer cells, and the underlying mechanism is related to the up-regulation of FBXW7 expression.