question: Applying the Technological Pedagogical and Content Knowledge 21 Century Learning framework during pandemic gives both chances and challenges for English pre-service teachers. Due to the complexity of integrating the TPACK and 21CL skills, many pre-service teachers are not yet equipped with the knowledge. This case study was to investigate twenty English pre-service teachers’ TPACK-21CL in Teaching Practicum. The data of this study were collected from lesson plans, reflective journals, and interviews. The findings indicate that (1) pre-service teachers demonstrated varying degrees of the knowledge and practice in designing lesson plan with TPACK-21CL framework;(2) the adoption of the TPACK-21CL framework into lesson plans had a positive impact on English pre-service teachers in terms of solving the problems and learning values. Teacher education programs, especially in a teaching practicum, should afford chances and challenges for English pre-service teachers to develop their TPACK-21CL framework into their lesson plan to effectively integrate technology, pedagogy, and content into their teaching in the future. © 2021. All Rights Reserved.