The plasma polishing process is one of the non-conventional techniques used to remove material at the atomic level from the substrate. During the polishing of the fused silica substrate, the process parameters, namely radio-frequency (RF) power, pressure ratio (SF 6 / O 2 ), and total pressure of the plasma chamber, are investigated and optimised for material removal rate (MRR) and % change in surface roughness (% ΔR a ) using response surface methodology. The optimum values obtained for MRR and % ΔR a are 0.012 mm 3 /min and 3.59, at RF power of 60 W, pressure ratio of 3, and total pressure of 14.3 mbar. The experimental results reveal that surface roughness slightly increases from 0.344 to 0.356 μm after plasma processing at optimised process conditions. Moreover, the plasma-processed fused silica substrate is characterised using field emission scanning electron microscopy and energy dispersive X-ray spectroscopy, which depict the presence of silicon, oxygen, and fluorine on the processed substrate.