The quality control of herbal medicines is key to their clinical efficacy. The multi-component and multi-effect characteristics of herbal medicines have prompted scholars to clarify various factors related to quality evaluation through various methods. Nevertheless, the relationship between chemical properties and their associated clinical efficacy is little reflected in the quality control techniques currently in use. To address the issue, a novel herbal quality standard system based on the efficacy-oriented Q-marker of the effect-constituent index (ECI) is promoted in this study, using Scutellariae Radix (SR), a widely used herbal medicine with anti-inflammation, anti-tumor, anti-viral and other therapeutic effects, as a case study. Combined with chromatographic analysis and bioassay, four Q-markers including baicalin, baicalein, wogonin and oroxylin A were selected based on the anti-inflammatory efficacy of SR. The ECI model of SR was constructed by combining the content determination of the Q-markers via ultra-high-performance liquid chromatography-triple quadrupole mass spectroscopy (UHPLC-QqQ-MS/MS) with the corresponding biological potency obtained from the anti-inflammatory effects on tumor necrosis factor (TNF)-α and interleukin (IL)-6 production. Correlation analysis showed that the ECI was significantly correlated with the measured anti-inflammatory activity (p < 0.01). The ECI exhibited a good ability to determine and predict the bioeffect-based quality grade for SR. Overall, the construction and application of the ECI for SR in this study provides a beneficial reference for quality evaluation methods of other herbs with distinct effects and active ingredients.