Based on the molluscicidal activity of ginkgolic acids (GAs) isolated from Ginkgo biloba L and synthetic GA analogues, a series of long chain, substituted at 4 and 5 position, salicylic acid derivatives, including the Z/E isomers and their saturated derivatives, were prepared. Their molluscicidal activities against the host snail Oncomelania hupensis were evaluated. The acute fish toxicity against the wild-type zebrafish of saturated derivatives was tested. The results and analysis of the structural-activity relationship revealed that the E-isomers and their saturated derivatives were better molluscicidal agents than their respective Z-isomers. Molluscicidal activities were increased with the growing of the alkyl chain lengths. Acute fish toxicity test indicated that the synthesized salicylic acid derivatives were much safer than niclosamide in field use. Key words: Hydrocarbyl substituted salicylic acid derivatives, synthesis, molluscicidal activity, Oncomelania hupensis, schistosomiasis, acute fish toxicity, zebrafish.