In order to explore new lead compounds against Penicillium italicum(PI) and Penicillium digitatum(PD) on citrus, fifteen 2-(2-cyanophenoxy)-2-fluoroacetamides were designed and synthesized using salicylonitrile, ethyl bromofluoroacetate, and amines as the main starting materials. Their structures were confirmed by 1HNMR, 13CNMR and MS. The antibacterial activity of these compounds against PI and PD was studied by the mycelial growth rate method. The results showed that these compounds had certain antibacterial activity against the tested strains. Among them, six compounds such as Ⅰa[ 2-(2-cyanophenoxy)-2-fluoro-N-phenylacetamide],Ⅰf[2-(2-cyanophenoxy)-2-fluoro-N-(thiazol-2-yl)acetamide] have 80% ~ 100% inhibitory activity against the two bacteria at the mass concentration of 200 mg/L. The antibacterial activity of compound Ⅰh is the best among all compounds. At the mass concentration of 50 mg/L, it’s inhibition rates of PI and PD are 60.96% and 53.95%, respectively. The inhibitions rates are more than 30% at the mass concentration of 25 mg/L. The activity of 2-(2-cyanophenoxy)-2-fluoroacetamides against tested strains is better than 2,4-D(2,4-Dichlorophenoxyacetic acid).