Anatase nanocrystals were successfully synthesized and deposited on protein keratin-type wool fibers with good compatibility and significant photocatalytic self-cleaning activity using the sol-gel process. Due to the low chemical resistance and liability to photo-degradation of protein materials, the effect of the acid catalyst used in the sol synthesis was studied. The sols were prepared using oxidizing and non-oxidizing catalysts, nitric acid and hydrochloric acid, respectively, for the hydrolysis and condensation reactions of the titanium dioxide precursor. The size distribution and crystallinity of the sols were characterized by X-ray diffraction spectroscopy and photon correlation spectroscopy. The compatibility of sol formulations and wool is thoroughly compared and discussed by analyzing fibers photo-degradation, surface morphology and self-cleaning properties including stain degradation and colorant decomposition. The UV absorption and mechanical properties of wool fibers before and after coating are also discussed.