In this study, the quercetin compound from Chromolaena sp was extracted by using ultrasonic-assisted enzymatic extraction (UAEE). Quercetin is a member of flavonoid compound with high anti-inflammatory and antimicrobial that usually used in skincare product to provide strong antioxidant and UV protection for human skin. Ultrasonic-assisted enzymatic extraction is a green technology, which expected to extract quercetin in shorter time, high extract yield and eco-friendly extraction technologies. There are two parameters studied namely; concentration of enzyme (cellulase) (0, 2, 4 and 6 %) and sonication time (0, 20, 40 and 60 minutes). The constant conditions are ratio of solid to liquid (1:10), duty cycle (25 %) and amplitude (60 %). Phytochemical screening present of more white precipitate in 40 minutes of sonication time and 4 % concentration of enzyme. From the experimental result, it was found that the optimum parameters obtained for the extraction of quercetin are 4 % of enzyme concentration and 40 minutes of sonication time for ultrasonic-assisted enzymatic extraction method (UAEE). Based on HPLC analysis, the concentration for quercetin extract using 4 % concentration of enzyme was 0.3671 mg/mL while the concentration of quercetin obtained using 40 minutes of sonication time was 0.3198 mg/mL. The band spectrum from FTIR analysis that presented in standard and sample show the similar pattern that represented by the functional group of primary amides and carbonyl stretching vibration. From the results in this study, it was proven that UAEE is a significant method for quercetin extraction from Chromolaena sp.