Cellulose from durian rind can be further utilized, including as advanced materials for the manufacture of bioplastics, as raw materials for bioethanol, and as raw materials for the pulp and paper industry. However, lignin hinders cellulose utilization. Lignin binds strongly to cellulose and hemicellulose, so it is necessary to prepare cellulose using a microwave-assisted delignification method. This study aims to examine the optimal conditions for preparing durian rind cellulose by varying delignification time and NaOH concentration to produce durian rind fiber with high cellulose content. This study uses Response Surface Methodology optimization techniques with a Central Composite Design, with 2 independent variables: NaOH concentration and time. The response or dependent variables observed were yield, cellulose content, hemicellulose content, and lignin content. The results of the study showed that cellulose content will increase along with the increase in NaOH concentration and the length of delignification time of durian skin, hemicellulose content will increase along with the increase in NaOH concentration and will decrease with the addition of delignification time, and lignin content will decrease along with the increase in NaOH concentration and will increase with the addition of delignification time. The optimum solution formula given is at a NaOH concentration of 0.79 M and a time of 33.25 minutes. The results of this study provide an alternative, environmentally friendly method for obtaining optimal cellulose.