Abstract: Objective To assess the efficacy of short-term intervention on psychoactive substance abuse(PSA) prevention among middle school students in Shenzhen city.Methods Totally 2480 students in 12 general middle schools were randomly selected and a month-long intervention on PSA, including distribution of education material and lectures on PSA prevention, was conducted among the students.Questionnaire surveys were carried out before and after the intervention to evaluate the changes in knowledge, attitude and behavior about PSA.Results No illegal drug use was reported by the students before and after the intervention.The reported rate of PSA significantly decreased(0.54% vs. 1.53%; χ²=12.647, P<0.05) and the average score for knowledge about PSA increased significantly(19.86±1.92 vs.18.89±2.46; t=608.01, P<0.05) after the intervention.The proportion of the students with curiousness to PSA decreased significantly form 5.85% to 2.78% after the intervention(P<0.05).Conclusion The short-term intervention on PSA prevention is effective in improving knowledge, attitude, and behavior about PSA among middle school students.