Abstract: As an important window material for the target chamber, the quartz substrate's cleaning is vital for its laser damage threshold. In this work, the quartz substrates polluted by evaporated silica-oil-and-grease were cleaned by CO2 laser and plasma and the damage thresholds were studied. The samples were characterized via the optical microscopy photo, the water contact angle, the optical transmittance and the laser damage threshold. The experimental results showed that the substrates could be well cleaned by low energy CO2 laser combined with vacuum subsequent plasma. After cleaning, the water contact angle of the quartz substrates decreased from 63 to 4, the transmittance increased from 92.3% to 93.0%, and the damage threshold increased from 3.77 J/cm2 to 5.09 J/cm2 when irradiated by 351 n