Sijunzi decoction (SJZD) is a Chinese classical formula to treat spleen qi deficiency syndrome (SQDS) and has been widely used for thousands of years.However,the quality control (QC) standards of SJZD are insufficient.Chinmedomics has been designed to discover and verify bioactive compounds of a variety of formularapidly.In this study,we used Chinmedomics to evaluate the SJZD’s efficacy against SQDS to discover the potential quality-markers (q-markers) for QC.A total of 56 compounds in SJZD were characterized in vitro,and 23 compounds were discovered in vivo.A total of 58 biomarkers were related to SQDS,and SJZD can adjust a large proportion of marker metabolites to normal level and then regulate the metabolic profile to the health status.A total of 10 constituents were absorbed as effective ingredients that were associated with overall efficacy.We preliminarily determined malonyl-ginsenoside Rb2 and ginsenoside Ro as the q-markers of ginseng;dehydrotumulosic acid and dihydroxy lanostene-triene-21-acid as the q-markers of poria;glycyrrhizic acid,isoglabrolide,and glycyrrhetnic acid as the q-markers of licorice;and 2-atractylenolide as the q-marker of macrocephala.According to the discovery of the SJZD q-markers,we can establish the quality standard that is related to efficacy.