As semiconductor manufacturing advances to sub-20-nm nodes, specification (size < 50 nm) for extremely fine particles on photomasks is getting more and more stringent. Photomask cleanliness, which seriously impacts manufacturing cycle time and productivity, is a serious challenge in the development of sub-20-nm node mask cleaning process. Several cleaning approaches, including the use of chemical and physical forces, are widely used in mask cleaning. In this study, we focus on the chemical force through zeta potential (ZP). ZP indicates the degree of repulsion between the particles and the mask surface (mostly quartz). In the nano-scale, stronger repulsion means easier removal of particles from mask surfaces. By controlling ZP of different chemicals from -10 mV to -150 mV in the cleaning process, the particle removal efficiency (PRE) is further improved by about 10%, especially for extremely fine particles. The ZP measurement methodology for different cleaning chemicals on quartz surface is also carried out. ZP is a helpful index in evaluating the performance of new chemicals for mask cleaning. To enhance photomask cleaning for sub-20-nm nodes, the chemical force needs to be increased because the physical force has been constrained to avoid pattern damages, especially when much smaller assistant features are commonly used to gain a greater lithography process window. How to choose a suitable cleaning approach for the next generation mask cleaning is very critical.