The aim of the present study was to investigate the functional role of syllables in sign language and how the different phonological combinations influence sign production. Moreover, the influence of age of acquisition was evaluated. Deaf signers (native and non-native) of Catalan Signed Language (LSC) were asked in a picture-sign interference task to sign picture names while ignoring distractor-signs with which they shared two phonological parameters (out of three of the main sign parameters: Location, Movement, and Handshape). The results revealed a different impact of the three phonological combinations. While no effect was observed for the phonological combination Handshape-Location, the combination Handshape-Movement slowed down signing latencies, but only in the non-native group. A facilitatory effect was observed for both groups when pictures and distractors shared Location-Movement. Importantly, linguistic models have considered this phonological combination to be a privileged unit in the composition of signs, as syllables are in spoken languages. Thus, our results support the functional role of syllable units during phonological articulation in sign language production.