Currently, the event-related potential (ERP)-based spelling device, often referred to as P300-Speller, is the most commonly used brain-computer interface (BCI) for enhancing communication of patients with impaired speech or motor function. Among numerous improvements, a most central feature has received little attention, namely optimizing the stimulus used for eliciting ERPs. Therefore we compared P300-Speller performance with the standard stimulus (flashing characters) against performance with stimuli known for eliciting particularly strong ERPs due to their psychological salience, i.e. flashing familiar faces transparently superimposed on characters. Our results not only indicate remarkably increased ERPs in response to familiar faces but also improved P300-Speller performance due to a significant reduction of stimulus sequences needed for correct character classification. These findings demonstrate a promising new approach for improving the speed and thus fluency of BCI-enhanced communication with the widely used P300-Speller.