Ultraviolet-ozone treated indium-tin-oxide (UV-ITO) glass substrates have been widely and unquestioningly used in the field of organic electronics to improve both device performance and stability. Evidence is presented here for rapid decay of common organic films such as N,N′-bis(naphthalen-1- yl)-N,N′-bis(phenyl)-benzidine (NPB), tris(8-hydroxy-quinolinato)aluminum (Alq3), and rubrene when they are in contact with an UV-ITO substrate. While the photoluminescence (PL) of these organic films deposited on an UV-ITO substrate decay rapidly under illumination; those on quartz substrates are comparatively much more stable. Results from X-ray and UV photoemission spectroscopies (XPS and UPS) further suggest that degradations of the rubrene films on UV-ITO substrate are mainly attributed to active oxygen species generated upon UV-ozone treatment. These reactive oxygen species on the UV-ITO surface behave as a reservoir of oxygen that interacts with rubrene and shifts its highest occupied molecular orbital (HOMO) level away from the Fermi level. This interaction induces a gap-state in the energy gap of rubrene, which acts as a charge recombination center. More importantly, enhanced stabilities of rubrene-based organic photovoltaic (OPV) devices are demonstrated when they are fabricated on gold-coated or trifluoromethane (CHF3) plasma-treated ITO. The presented works shows that the commonly used UV-ITO substrate is a threat to the stability of addlayer organic semiconducting films.