The aim of this study was to compare the effectiveness of two teaching approaches for senior secondary biology students to learn about the nature of science (NOS): the History of Science (HOS) approach, which is the most commonly used approach in Hong Kong schools, and the Socio- scientific Issue (SSI) approach, which develops students’ understanding of NOS through analysis of socio-scientific issues. This study was motivated by the consistent reports by the Hong Kong Examinations and Assessment Authority (HKEAA) on the poor performance of Grade 12 Biology students in the Hong Kong Diploma of Education Examination (HKDSE) regarding their understanding of the Nature of Science (NOS). From the literature, the SSI approach presents a viable alternative in improving students learning of NOS. Three research questions were construed. 1) Could the SSI or HOS approach enhance Hong Kong senior secondary students’ understanding of major tenets of NOS? 2) Which approach, SSI or HOS, could help Senior Secondary Biology students develop more informed conceptions of major NOS tenets? 3) Are there any influences of gender or biology performance on students’ learning of NOS using either approach?This research was based on a quasi-experiment design. The sample consists of 67 secondary students from four intact classes, two of which were biology classes at Grade 11 and two biology classes at Grade 12. They were divided into two treatment groups (HOS and SSI), with each group comprising one Grade 11 and one Grade 12 class. All students received a pre-test consisting of 10 open-ended questions based on the Views of Nature of Science form D+ (VNOS-D+) instrument to test students’ understanding of NOS before the intervention. After this, both groups went through a 3-day learning process to enhance their understanding of NOS. The only difference was that one group was taught through the HOS approach, while the other group received the intervention by using SSI. After almost two weeks of the