Individual interest in school science lessons can be defined as a relatively stable and enduring personal emotion comprising affective and behavioural reactions to events in the regular science lessons at school. Little research has compared the importance of different factors affecting students' individual interest in school science lessons. The present study aimed to address this gap, using a mixed methods design. Qualitative interview data were collected from 60 Hong Kong junior secondary school students, who were asked to describe the nature of their interest in science lessons and the factors to which they attribute this. Teacher interviews, parent interviews, and classroom observations were conducted to triangulate student interview data. Five factors affecting students' individual interest in school science lessons were identified: situational influences in science lessons, individual interest in science, science self-concept, grade level, and gender. Quantitative data were then collected from 591 students using a questionnaire. Structural equation modelling was applied to test a hypothesised model, which provided an acceptable fit to the student data. The strongest factor affecting students' individual interest in school science lessons was science self-concept, followed by individual interest in science and situational influences in science lessons. Grade level and gender were found to be nonsignificant factors. These findings suggest that teachers should pay special attention to the association between academic self-concept and interest if they want to motivate students to learn science at school.