[Purpose/significance] The research in the field of health informatics is developing rapidly, but the con? struction and research of theoretical system is still deficient in this field. This research aims to build a systematic theo? retical framework for health informatics research by reviewing the current situation of empirical-based theoretical ap? plication research in health informatics abroad, so as to provide a reference for the development of paradigm for related research. [Method/process] A total of 91 empirical-based research papers on theoretical applications in health infor? matics were retrieved from Web of Science, PubMed, and Scopus databases, and the theoretical sources, types, applica? tion objects, and research themes in the studies were analyzed using bibliometric methods and content analysis, and then cluster and condense the framework of the theoretical application research in health informatics. [Result/conclu? sion] The results showed that health informatics theoretical research focuses on the application of theories from related disciplines or interdisciplinary fields, while lacks the exploration and research of basic theories. Moreover, the research on the application of theories lacks systematicness, wholeness, and logic. This study integrates the existing researches on the application of theories in health informatics by condensing a theoretical application research framework that con? tains four elements (user, information, system, and environment) to provide a reference for the theoretical foundation and applied research of health informatics.