Although Sign Languages are gestural languages, the fact remains that some linguistic information can also be conveyed by spoken components as mouthing. Mouthing usually tend to reproduce the more relevant phonetic part of the equivalent spoken word matching with the manual sign. Therefore, one crucial issue in sign language is to understand whether mouthing is part of the signs themselves or not, and to which extent it contributes to the construction of signs meaning. Another question is to know whether mouthing patterns constitute a phonological or a semantic cue in the lexical sign entry. This study aimed to investigate the role of mouthing on the processing of lexical signs in French Sign Language (LSF), according the type of bilingualism (intramodal vs. bimodal). For this purpose, a behavioral sign-picture lexical decision experiment was designed. Intramodal signers (native deaf adults) and Bimodal signers (fluent hearing adults) have to decide as fast as possible whether a picture matched with the sign seen just before. Five experimental conditions in which the pair sign-mouthing were congruent or incongruent were created. Our results showed a strong interference effect when the sign-mouthing matching was incongruent, reflected by higher error rates and lengthened reaction times compared with the congruent condition. This finding suggests that both groups of signers use the available lexical information contained in mouthing during accessing the sign meaning. In addition, deaf intramodal signers were strongly interfered than hearing bimodal signers. Taken together, our data indicate that mouthing is a determining factor in LSF lexical access, specifically in deaf signers.