The goal of this study is to report the antischistosomal activity of liposomes containing 3-(4-chloro-benzyl)-5-(4-nitro-benzylidene)-imidazolidine-2,4-dione (FZ4-LPSF). The solubility of FZ4 at different pH values was evaluated. Liposomes containing FZ4 (Lipo-FZ4) were obtained through lipid thin film method and FZ4 content was detected at 347 nm. The antischistosomal activity was investigated in Swiss mice infected with about 80 cercariae of Schistosoma mansoni. The treatment of animals was performed 49 days after infection with i.p. daily dose of 10 mg/kg for 5 days. The effect of FZ4 was evaluated by the number of eggs in faeces through Kato-Katz method. Animals were killed 64 days post-treatment and the hepatic and portal mesenteric vessels were perfused to recover worms. Oogram patterns were determined in small intestine. FZ4 is more soluble at pH 12 (14.52 mg/mL) than pH 2 (0.53 mg/mL). The two carboxylic groups presented at the imidazolic ring of FZ4 are electron acceptors, which confer a Lewis acid character to FZ4. Similar effects are observed for the p-chloride placed in the benzyl ring and the p-nitro at the benzylidene radical, both presenting positive σp electroattractor effects of 0.24 e 0.78, respectively. The entrapment efficiency of FZ4 into liposomes (0.5 mg/ml) was 93%. Parasitological analysis revealed a reduction of 9.53% and 16.78% on the number of eggs in faeces for FZ4 and lipo-FZ4, respectively. On the oogram pattern no immature eggs were found and an increase in mature eggs was observed with both treatments FZ4 (31.66% ± 10.6) and lipo-FZ4 (46.10% ± 11.67). A remarkable increase on dead eggs was detected after treatment with FZ4 (63 % ± 15.03) and lipo-FZ4 (52.22% ± 10.57). Remarkable worm reductions of 61.39% and 48.83% were observed with free FZ4 and lipo-FZ4 treatments, respectively. The treatment of animals infected with S. mansoni with lipo-FZ4 was as efficient as free FZ4 and the antischistosomal effect of the lipo-FZ4 was evidenced.