The response surface method was used to optimize the quercetin and cyanidin content experimental parameters for the ultrasonic-assisted extraction of phenolics from Pyracantha coccinea. The optimal conditions were an extraction time of 97 and 93 min, ethanol concentration of 71 and 79% (v/v), HCl concentration of 1.55 and 1.52 mol/L, liquid-solid ratio of 12.2 and 12.6 mL/g for determining the quercetin and cyanidin contents, respectively. The predicted quercetin and cyanidin contents were 2.30 and 4.01 mg/g, respectively. The experimental values agreed with those predicted at the 95% confidence level, which indicates the response surface method was suitable for optimizing the ultrasound-assisted extraction of phenolics from P. coccinea. The scavenging effects of cyanidin and quercetin in P. coccinea extract, which extracted at optimum conditions, on free radicals were investigated using the Fenton oxidation. It was also demonstrated that cyanidin had more effective free radical scavenging activity than quercetin.