Oil palm mesocarp fiberis a by-product of the palm oil pressing process, which has great potential if used as a second-generation biofuel raw material. The main components of oil palm mesocarp fiber are cellulose, hemicellulose, and lignin commonly called lignocellulose. Cellulose is the most valuable component to be utilized in the bioenergy sector. However, the oil palm mesocarp fibers lignin layer, which binds cellulose and restricts cellulose accessibility, makes it difficult to use. Ozone pretreatment is considered to be an alternative and effective method of lignin breakdown. This study compares the ozonation, ultrasonic, and hybrid ozonation-ultrasonicmethods used to degrade lignin in oil palm mesocarp fibers. The operating conditions were set at pH (3, 4, 5, 6, 7, 8, 9, 10, 11), flow rate (1, 2, 3, 4, 5) L min-1, for (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100) minutes, at 29±1 oC. The research indicates that using ozonation-ultrasonic hybridization results in a more significant degradation of lignin than using ozonation and ultrasonics individually. In this investigation, the hybrid ozonation-ultrasonic treatment gives the best lignin degradation results and the highest quantities of cellulose, reaching 91.99% after 60 minutes at a temperature of 29±1 oC, a pH of 9, and a flow rate of 2 L.min-1. Meanwhile, the degradation of lignin using ozone treatment is 72.75%, and ultrasound only 47.70%. Cellulose with the highest purity is 89.71%.