The development of subject-specific word lists to assist EFL learners is becoming popular, as is the utilization of CLIL to teach English in academic areas of science. The purpose of this research was to investigate the effects of the instruction of English Science Textbooks Word Lists (ESTWL) and the CLIL approach on the Science Vocabulary Knowledge and Science Content Knowledge of Thai EFL students. A mixed-methods research design was employed to gather both quantitative and qualitative data using ESTWL-CLIL lesson plans, a Science Vocabulary Knowledge test, and a Science Content Knowledge test. All research instruments were validated by both content and language experts. The target groups were 3 levels of secondary school students studying at a large secondary school in Bangkok. The research findings were as follows: 1) the mean scores of the students in the three groups increased by a statistical significance of 0.05 for both vocabulary knowledge and science content knowledge after the implementation of the intervention, and 2) the qualitative results indicated that all students perceived the instruction of ESTWL and the CLIL approach to be positive. The study suggested a vocabulary pedagogy for science and language teachers for use in CLIL environments.