The aim of the study was to discover the contribution of students' interest in school biology, as well as their self-efficacy and attitudes towards different science subjects and mathematics when explaining students' orientation towards biology-related careers at upper-secondary school. The data of 321 K-11 students (49% women) were analyzed. Human biology and gene technology was the most interesting topics of biology among the students. The students' self-efficacy belief was highest in geography and lowest in mathematics. Male students had higher self-efficacy in mathematics and science subjects, but in biology, no gender difference was found. Self-efficacy in biology and geography intercorrelated, as did self-efficacy in mathematics, physics, and chemistry. Regression analysis revealed that interest and self-efficacy in biology and positive attitudes to biology as school subjects explained girls' orientation towards a biology-related career, as did low self-efficacy in physics and geography. For boys, only interest in biology, positive attitudes to biology as a school subject, and self-efficacy in biology explained their biology-related career orientation. The students' attitudes and self-efficacy beliefs in science subjects should be taken into account in secondary school biology education, because gender stereotypes and low self-efficacy beliefs may affect students' future career plans.