Poly(methyl methacrylate) (PMMA) has been widely used for intraocular lenses (IOL) but may lead to posterior capsule opacification (PCO) after implantation due to its undesirable hydrophilicity and surface morphology. A novel methacrylisobutyl polyhedral oligomeric silsesquioxane-co-poly methyl methacrylate copolymer (MA POSS–PMMA) was synthesized by a free radical polymerization method to improve its material properties and cytocompatibility. Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and proton nuclear magnetic resonance spectroscopy (¹H NMR) measurements demonstrated the successful synthesis of MA POSS–PMMA copolymer. The incorporation of MA POSS greatly changed the crystal structure, surface wettability, optical transmission and cytocompatibility of PMMA. XRD peaks at 2θ ∼ 38.5, 44.7 and 66.1° indicated that a portion of the MA POSS molecules had aggregated and crystallized. Furthermore, larger aggregates are formed at higher MA POSS contents. The optical transmission of the copolymers was up to 99%, which was better than pure PMMA. The hydrophilicity and morphology of the IOL surface were characterized by static water contact angle and atomic force microscopy. Results revealed that MA POSS rendered the surface more hydrophobic and with higher roughness than the pure PMMA. Biocompatibility of copolymers with human lens epithelial cells (HLECs) was further evaluated by morphology and activity measurements in vitro. More HLECs adhesion and better spreading morphology on the surfaces of MA POSS–PMMA copolymers than that on PMMA was shown.