Polysiloxanes have shown exquisite properties for fabrication of microstructures for various biomedical and biotechnological applications. Nevertheless, their biocompatibility in terms of cell adhesion and survival ability is controversial. A simple polysiloxane modifying procedure that reproducibly enhances cell adhesion was proposed. Sonication of the hybrid organic-inorganic polymer of polysiloxane type, Ormocomp, in potassium hydroxide (KOH)/ethanol solution enhanced adhesion and subsequent survival of a panel of four cell lines. Characterization of surface properties of untreated and KOH-treated Ormocomp coatings has revealed considerable negative charge of Ormocomp substrates based on measurements of zeta potentials. KOH treatment did not modify surface morphology as visualized by scanning electron microscopy, but it resulted in alteration in both chemical composition according to SIMS analysis and hydrophilicity evaluated by static water contact angles. The results suggest that the failure of the adherent cells to survive on Ormocomp coatings is related to cell adhesion. The negative surface charge of Ormocomp substrates may be one of the influencing factors; however, the modification of surface chemistry mediated by KOH and the resulting increase in hydrophilicity accompanied by modification of protein adsorption are more likely responsible for enhanced cell adhesion and survival on Ormocomp coatings. KOH treatment thus may serve as a simple, cost-effective procedure modifying polysiloxane-type polymers that leads to reproducible enhancement of cell adhesion.