In this article, the effect of enzyme treatment using neutral cellulase on the color fading property of cotton denim fabric was studied. Four enzyme processing parameters namely treatment temperature, treatment time, pH value, and agitation were considered. To investigate the optimum condition for the enzyme treatment, an orthogonal analysis was used and, based on the K/S summation value (K/S Sum), the optimum condition for enzyme treatment in this study was treatment temperature ¼ 50 C; treatment time ¼ 30 min; pH value ¼ 8; and agitation ¼ 50 steel balls (simulated mild agitation) for the best color fading achievement with desired worn and aged effect. Meanwhile, the level of importance based on the orthogonal analysis was in the order: treatment temperature > treatment time > agitation > pH and the effect of each processing factors was also discussed. In addition, other properties like CIE Lab values, weight loss, and color fastness to laundering and crocking were also evaluated.