Smoking and consuming alcohol remain hazardous acts to health, which are important to prevent in adolescents. Prosocial behavior has increasingly being noticed to be related with substance use. This study investigated the association between the trying of smoking and alcohol with prosocial behavior among school-going adolescents in Terengganu, Malaysia. This cross-sectional study was conducted among 732 school adolescents aged between 13 and 18 years from 12 secondary schools in Terengganu. Cluster sampling was applied. A validated questionnaire adopted from Global Health School Survey (GSHS) was used and prosocial behavior was assessed using the validated Malay self-rated version of Strength and Difficulty Questionnaire (SDQ). Data were analyzed using SPSS ver25, using multiple logistic regressions for both dependent variables of ever smoking and ever alcohol drinking. Ever smoking was significantly inversely associated with prosocial behavior (p = 0.010, OR: 0.84, CI: 0.74, 0.96); together with other significantly associated factors; namely older age, male gender, poorer family income, and smoking in immediate family members. However, there was no association of the between prosocial behavior with ever alcohol drinking (p = 0.628). Prosocial behavior is negatively associated with the trying of smoking in adolescents. Future longitudinal study should be done to investigate the effects of promoting prosocial behavior among adolescents towards the hazardous act. © 2020 Published by Elsevier Ltd.