The purpose of this study is to investigate the effect of argumentation, during the hypothetico-deductive reasoning (HDR) process in the problem-based learning (PBL) approach, on nursing students' achievements and to determine the argumentation levels in the biochemistry course on the topic of endocrine and nervous systems. The participants consisted of first-year nursing students studying in the Faculty of Health Sciences of a state university in Turkey (N = 189). This study used a single group pre- and post-test research design. Three scenarios associated with daily life about endocrine and nervous systems were developed and applied. The 'Endocrine and Nervous System Achievement Test (ENSAT)' was used as the data collection tool. In addition, the argumentation levels of the students were also examined during the implementation process. The results concerning the content and statistical analyses of ENSAT showed that the use of this hybrid method increased the students' sound and partial understandings and that there was a statistically significant difference in favour of the post-test. Furthermore, the results also showed that the level and number of argumentations increased from the first scenario to the last scenario.