In search of novel antifungal agents from natural renewable biomass resources, twenty-two (E)-longifolene-derived tetralone oxime ether compounds were synthesized. Their structures were confirmed by IR, 1 H-NMR, 13 C-NMR, ESI-MS and elemental analysis. The preliminary evaluation of in vitro antifungal activity showed that, at the concentration of 50 μg/ mL, eight target compounds exhibited better antifungal activity than that of the positive control commercial fungicide chlorothalonil against Gibberella zeae, in which compound 5 a held excellent inhibition rate of 85.6 % against Fusarium oxysporum f. sp. Cucumerinu, and compound 5 d displayed a good and broad-spectrum antifungal activity. Furthermore, a preliminary three-dimensional quantitative structure-activity relationship (3D-QSAR) study was carried out by the CoMFA method for the inhibitory activity of the target compounds with aromatic R substituents against G. zeae, and a reasonable and effective 3D-QSAR model (r 2 = 0.992, q 2 = 0.523) was established.