Cancer is a leading cause of death globally and the second cause of death in developed countries. Having a rising incidence, skin cancer is the most prevalent cancer in Iran. Long-term UV radiations, particularly during childhood and adolescence, is a major cause of skin cancers. The Theory of Planned Behavior as the most precise indicator of behavior, contains motivational factors affecting behavior. This theory has been successful in predicting factors related to chronic diseases, especially cancer. As this model was successful in assessing sun-protective behaviors in previous studies, this study was designed to figure out how a theory-based educational intervention can affect the skin cancer prevention practices of Iranian female high school students. This experimental investigation was carried out 2019–2020 using multistage cluster sampling method on 400 female high school students in Fasa, Fars, Iran. A questionnaire consisting of demographic data and a questionnaire including the components of the Theory of Planned Behavior was used to assess skin cancer preventative behaviors of both the trial and control groups of the study. An educational program based on the Theory of Planned Behavior was held for the experimental group for eight weeks regarding skin cancer preventive behaviors. The two groups completed questionnaires three months following the intervention for a second time. The study's findings revealed that prior to the intervention, there was no considerable distinction between the two study groups with regard to knowledge, attitude, subjective norms, perceived behavioral control, behavioral intentions, and skin cancer prevention behaviors; yet, three months later, the experimental group demonstrated increases in each of the mentioned variables with a significant difference. In contrast, the control group showed no discernible difference. The findings of this investigation highlighted the success of the Theory of Planned Behavior for designing educational interventions aimed at encouraging skin cancer prevention in a population of female high school students.