We investigated the influence of grapheme familiarity and native language grapheme-phoneme correspondences during second language lexical learning. Native English speakers learned Russian-like words via auditory presentations containing only familiar first language phones, pictured meanings, and exposure to either Cyrillic orthographic forms (Orthography condition) or the sequence (No Orthography condition). Orthography participants saw three types of written forms: familiar-congruent (e.g., -[kom]), familiar-incongruent (e.g., -[r?t]), and unfamiliar (e.g., -[fil]). At test, participants determined whether pictures and words matched according to what they saw during word learning. All participants performed near ceiling in all stimulus conditions, except for Orthography participants on words containing incongruent grapheme-phoneme correspondences. These results suggest that first language grapheme-phoneme correspondences can cause interference during second language phono-lexical acquisition. In addition, these results suggest that orthographic input effects are robust enough to interfere even when the input does not contain novel phones.