Objective To explore the comprehensive quality evaluation of Panax notoginseng based on high performance liquid chromatography (HPLC) multi-component quantification combined with grey relational analysis. Methods HPLC was used to simultaneously determine the contents of notoginsenoside R1, ginsenoside Rg1, Re, Rb1, and Rd in Panax notoginseng samples from different origins and different commercial specifications. A comprehensive quality evaluation model was established by combining the grey relational method. Results The established method simultaneously determined the contents of notoginsenoside R1, ginsenoside Rg1, Re, Rb1, and Rd, with good methodological investigation results. The grey relational method could distinguish between samples from authentic origins, qualified samples, and unqualified samples. Conclusion The fusion model of HPLC multi-component quantification and grey relational analysis was constructed to accurately evaluate the quality of Panax notoginseng, providing a scientific evaluation basis.