The invention relates to a synthetic method of methylene ether urushiol hydroxamic acid derivatives with (histone deacetylase) HDAC inhibitory activity. Unsaturated urushiol is taken as a raw material, and oxidative polymerization of the urushiol is blocked through an etherification reaction; hydroxamic acid groups are introduced to tail parts of side chains of the urushiol thorugh a Diels-Alder reaction, a hydrolysis reactions, a hydroxylation reaction and the like; and in addition, different pharmacological groups such as nitro groups, hydroxyl groups and the like are introduced into benzene rings or alkyl chains, so that three methylene ether urushiol hydroxamic acid derivatives are synthesized. The three compounds can be well combined with active pockets of HDAC, can form stable hydrogen bonds with residual groups of the HDAC for interaction, and can be stably chelated with Zn<2+> at the bottom of the active pockets, so that good HDAC inhibitory activity is achieved. The median inhibitory concentrations (IC50) of the three compounds on HDAC 2 and HDAC 8 are equivalent to the IC50 value of an HDAC inhibitor SAHA approved by the Food and Drug Administration (FDA). The three compounds can be applied to clinical antitumor drugs and have extremely high additional values, and the synthetic method can be a novel technology for clinically developing novel phenol-based HDAC inhibitors.