The main purpose of this study is to explore the epistemological problems underlying pre-service chemistry teachers’ aims in using practical work, i.e., individual or small group object manipulation or observation, in school science. Twenty-two pre-service chemistry teachers participated in this study. Qualitative data collection tools included participants’ reflections about some practical work cases; participants’ practical work plans; responses given to open-ended questions about practical work, scientific inquiry, the epistemology of science, and science teaching approaches such as discovery and inquiry based learning; and follow-up interviews. Through the qualitative analysis of the data, participants’ aims were grouped under three main themes, which included six categories: providing learning by discovery to students, serving to verify scientific theory, making scientific theories concrete, developing students’ scientific process skills, providing learning about the nature of science, and creating curiosity and motivation towards science. Arguments related to any epistemological problems underlying some of these aims are presented in the Results and discussion section. Based on the results, conclusions were made about the sources of these epistemological problems, why the epistemology of science should be considered explicitly when teaching the science teaching approaches and using the practical work, and why “teaching nature of science implicitly” failed.