Abstract: Self-medication may result in several consequences such as pathogenicity or even mortality. The present study aimed to prediction cognitive factors related in self-medication among college students based on prototype/willingness model. It was crosses sectional study investigating 237 students of Department of Health Education, School of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran during 2015. A structured questionnaire was applied for collecting data and data were analyzed by SPSS Version 21 using chi-square, t-test, bivariate correlations and regression at 95% significant level. The mean age of respondents was 21.9 years [SD: 2.41], ranged from 18-30 years. Almost 45.1% of the participants had self-medication. There was a significant correlation between health insurance and self-medication (p = 0.004). In addition, it was a significant correlation between smoking and self-medication (p = 0.003). However, there was no significant difference between self-medication and gender, school of study, educational level, marital status and living in dormitory. Attitude, subjective norms and prototype variables were statistically significant for predicting self-medication which they were accounted for 41% of the variation in self-medication behavior intention and 15% of the variation in behavior willingness to self-medication. The findings showed that the attitude, subjective norms and intention were more powerful predictors of self-medication. It seems essential to consider these factors to planning interventions to get better results.