Abstract: For the evolutionary history of ancient and modern populations in East Asia over the past five thousand years, previous research of molecular anthropology has achieved some results, which has attracted the attention of academia and the public, but there are also many ambiguities, deviations or errors, which have caused a lot of controversy. At present, the spatial-temporal resolution of the basic data used in research of molecular anthropology has been greatly improved. For example, the resolution of phylogenetic tree of paternal Y-chromosome has been refined to about 70 years, and researchers had identified many paternal genetic sub-branches that are special to a population or a paternal family. In addition, ancient DNA data are also accumulating rapidly. The fine genetic pedigree of molecular anthropology and the concepts and theories of cultural anthropology are expected to be combined with historical research and applied to the study of micro issues. This paper attempts to discuss its possibility and methodology with two topics as examples, including: 1) in the near ancient period, the origin of Aisin Gioro family and Gioro Hara, and the change and rise process of Jurchen tribes in the Yuan and Ming Dynasties; 2) In early ancient period, whether the duke of Zhao and King Wen of Zhou families had the same origin recently, the source of Shang culture tradition among Zhao family and the diversity within the Ji Zhou tribe. It is expected that the discussion in this paper will be helpful to the further multidisciplinary cooperative research in the future.