Aim of this research is to examine the effect of the use of the socio-scientific argumentation method on students' entrepreneurial perceptions in the middle school science course. In the study, quasi-experimental design with pretest-posttest control group, as one of the quantitative research, was used. Experiment and control groups were formed from students who were studying in four classes in a determined middle school in the 2017-2018 academic year. In this study, lessons were taught with the socio-scientific argumentation method in the experiment group while Turkish Science Education Program activities and application continued to be used in the control group. The Entrepreneurship Perception in Science Education Scale was used as the data collection tool in the study. The scale was developed in order to determine secondary school students' entrepreneurship perceptions. The scale consists of 5 factors and 28 items. Findings of research indicated a significant score difference in favor of the experiment group. In addition, findings of sub-factor scores also indicated significant score differences in favor of the experiment group According to the results of the study, socio-scientific argumentation method positively affected the students' entrepreneurship perception. Furthermore, results show that socio-scientific argumentation method positively affected the students' self-esteem, innovation perception and creativity, leadership and tendency to stand out, social skills and group work, and risk taking tendency. Socio-scientific argumentation method might also have influenced the entrepreneurship characteristics which is a learning outcome for students according to the 2013 and 2018 Turkish Science Education Program.