The high price of the reference substances is an obstacle for the HPLC analysis of Lonicerae Japonicae Flos. To solve this problem, a new method based on the standard reference extract (SRE) was proposed. In this study, the extract of Lonicerae Japonicae Flos was calibrated, and the long-term stability was investigated. Different concentration solutions of SRE were prepared for establishment of the calibration profiles, and 6 organic acids were determined. T-test was used for the comparison of the determination results via reference substances and SRE, and the results demonstrated that there is no significant difference between the two methods. The presented method can be used for the quality control of Lonicerae Japonicae Flos, and will also offer reference to resolve similar problems.