The high efficiency particulate air filter is used widely to remove particulates and microorganisms from the air stream. However, the filter may become a source of microbes if those retained microorganisms proliferate and re-entrain back into the filtered air. This study demonstrates that such a problem can be handled effectively by using photocatalytic reactions to inactivate those confined microorganisms. A 60-100% microbe reduction can be achieved for a wide variety of microorganisms to provide better indoor air quality for hospitals, offices, and domestic applications.