The present study sought to examine the relationship between Chinese high school students’ academic self-efficacy and their academic-related boredom. Another objective was to explore the moderating effects of mono-amine-oxidase type A (MAOA) gene polymorphism on this relationship. In a sample of 514 Chinese high school students, we measured their academic self-efficacy and academic-related boredom from Grades 10 to 12. In addition, we collected their DNA. Data were analyzed by using a linear mixture model. The results indicated that students’ academic self-efficacy negatively predicted their academic-related boredom. The relationship between academic self-efficacy and academic-related boredom was more reliable for students with the 3-repeat allele than for the students with the 4-repeat allele. The findings suggested that the functional polymorphism of MAOA gene moderated the relationship between academic self-efficacy and academic-related boredom.