Abstract: To solve the drawbacks of easy protein adsorption and fast drug delivery for traditional poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogel corneal contact lens, β-cyclodextrin-hyaluronan (β-CD-crHA) as a functional derivative was used to modify pHEMA hydrogel for improving the performance of tear protein adsorption inhibition and sustainable drug delivery. The composition, morphology, water contact angle, water absorption, light transmittance, tensile property, tear protein adsorption, and loading and delivery of diclofenac sodium were systematically characterized by proton nuclear magnetic resonance spectrometer (¹H-NMR), Fourier transform infrared spectrometer (FT-IR), atomic force microscope (AFM), contact angle instrument, ultra-violet spectrophotometer, and electronic universal testing machine, etc. Results showed that β-CD was successfully bonded on the molecular chain of hyaluronan and the substitution degree was calculated to be 18.2%. Moreover, β-CD-crHA was also proved to incorporate into the matrix of pHEMA hydrogel after crosslinking with aminated polyethylenimine via amidation reaction. The increase of β-CD-crHA content remarkably enhanced the hydrophilicity of pHEMA hydrogel, which effectively reduced the adsorption of lysosome and albumin by 51.3% and 34.8% respectively, in comparison to pure pHEMA hydrogel. Meanwhile, the introduction of β-CD-crHA into pHEMA hydrogel significantly increased the loading capacity of diclofenac sodium and sustainable drug delivery as well. However, β-CD-crHA didn't damage the basic properties of pHEMA hydrogel, such as light transmittance and tensile strain. Therefore, pHEMA/β-CD-crHA hydrogel, which effectively improves the tear protein adsorption inhibition and sustainable drug release of traditional pHEMA hydrogel corneal contact lens, is a promising corneal contact lens material for ophthalmic disease.