In this study, guava mash was preliminary treated by ultrasound and then by cellulase preparation for juice processing. Response surface methodology was applied to optimize the conditions of the biocatalytic treatment. The optimal conditions of cellulolytic treatment were enzyme concentration of 0.12%(w/w) and treatment time of 57 minutes. Under these conditions, the extraction yield achieved maximum of 65.7% and this value was 21.2% higher than that in the control sample. In addition, the guava juice quality was improved. The levels of total sugars and phenolics were increased 13.5% and 16.4%, respectively in comparison with those in the control sample. Guava mash treatment by ultrasound and cellulase preparation reduced the ascorbic acid content in the obtained juice but its antioxidant activity increased 19.7%(evaluated by 2, 2’-azinobis-3-ethylbenzothiazoline-6-sulfonic acid method) and 11.5%(evaluated by ferric ion reducing antioxidant power method) compared to that in the control sample.