Lycopene is a powerful antioxidant and a valuable potential combined that today it is tried to increase achieving it by using tomato and its products. In this study, the effect of the sample weight of 0.5, 1 and 1.5 grams at different ultrasound waves times of 0, 30 and 60 min and the cellulase enzyme concentration of 20, 40 and 60 unit on extraction of lycopene from tomato waste was investigated and process optimization was performed using response surface methodology. The design of statistical analysis showed that the amount of sample, the time of using of ultrasound waves and enzyme concentration has a significant effect on the amount of lycopene extraction. Optimal amount of sample, ultrasonic time and enzyme concentrations were obtained 1.5 g, 30 minutes and 40 units by statistical analysis using response surface methodology (RSM). Based on the results, using integration processes of ultrasonic and enzymatic is suitable for the extraction of lycopene because the lycopene can be extracted without the use of organic solvents which have negative effects on health and it is not economical. The extraction of lycopene only with ultrasonic waves causes isomerization and destruction of lycopene, but if it is used as a pre-treatment of enzymatic extraction process leads an increase in extraction of lycopene.