An association between a common deletion comprising the late cornified envelope LCE3B and LCE3C genes (LCE3C_LCE3B-del) and psoriasis has been reported in Caucasian and Asian populations. To investigate whether this deletion plays a role in the genetic of psoriasis in Tunisian population, we determined the LCE3C_LCE3B-del genotype in 180 Ps patients and 208 healthy controls from different regions of Tunisia. The LCE3B and LCE3C gene variant was determined in the patients through PCR amplification and the SPSS software package. The frequency of the LCE3C_LCE3B-del was similar between patients and healthy controls. Subanalyses by family history revealed that the frequency of LCE3C_LCE3B-del was significantly higher in patients with a positive family history than in control individuals, as well as in individuals with a positive family history versus those without in the case cohort. However, no significant difference was observed between psoriatic patients with no family history and controls. We also evaluated the relationship between LCE3C_LCE3B-del and PSORS1. No significant epistatic effect was observed suggesting that there was no significant epistasis of the two loci in the Tunisian population. Our findings indicate that the LCE3C_LCE3B-del might play a role in familial psoriasis in the Tunisian population.