The paper aims to explore basic steps, regulation and data analysis methods of semi-structured and in-depth interview studies of clinical research in traditional Chinese medicine (TCM), and to provide some helpful information obtained from the examples for decision making in TCM research field. A pilot study was made with eight interviewees and, based on which, a formal one with twelve interviewees was done in this study. All the recordings were transcribed into verbal manuscripts, categorized into different archives and labeled by letter from A to T. Grounded theory for analyzing qualitative data was used in this study, and cross-case analysis was also made on the basis of case-by-case analysis results. Nine theories with central categories were constructed by three coding procedures from grounded theory. Three kinds of relationships, three types of optimized attitude, and three concerns were obtained from the example study. Nine analyzing conceptual graphs and nine theories related to optimization of TCM clinical research program were established finally. The researchers of large national studies were included as interviewees in the study. A comprehensive and critical data analysis from twelve interviewees for in-depth interview was conducted in accordance with current international qualitative research, and a response theory model focused on optimization of TCM clinical research program was established. The study laid the foundation for using semi-structured and in-depth interview for TCM clinical research.