Abstract: We evaluated the killing effects of water extracts of six Chinese herbal medicines on Crytocaryon irritans in vitro, and found out that treating theronts for 5 min with 7.14 mg·mL^–1 of Fructus mume, Areca catechu, Dryopteris setosa and Punica granatum, respectively, had rendered the theronts mortality rate of 100%. Moreover, treating tomonts with the above water extracts at a concentration of 28.57 mg·mL^–1 for 4 h could lead to the tomonts mortality rate of over 84.1%. To evaluate the preventive effect of water extract of F.mume on C.irritans infection, we studied the weight gain, lysozyme activity, hemolytic activity of alternative pathway CH50 (ACH₅₀), number of fish trophozoites and mortality rate of Epinephelus lanceolatus♀×E.fuscoguttatus♂ after having fed with water extract of F.mume for 14 d. No significant difference was observed in weight gain and hemolytic activity of ACH₅₀ between medicine groups and control group (P>0.05). In addition, lysozyme activity was all significantly higher than that in control group (P<0.05), and number of trophozoites after infection with C.irritans was significantly lower than that in control group (P<0.05). Furthermore, the survival rate in medicine groups (11.4 g·kg^–1, 6.84 g·kg^–1, 3.42 g·kg^–1) and the control group were 40%, 20%, 46.67% and 0% with lethal dose infection, respectively. It is indicated that F.mume has developmental prospects for preventing C.irritans infection.