The T300A variant is among the most Crohn's disease (CD) associated genetic variants. The aim of our study is to bring a first insight about the contribution of the T300A variant in a cohort of Algerian CD. In a case/control design, 118 Algerian CD patients and 161 unrelated healthy subjects were genotyped for the T300A variant using the allelic discrimination test by Applied Biosystems Taqman^® genotyping technology. A serological analysis was carried out using Biosystems™ ELISA kit for the assessment of the anti-Saccharomyces cerevisiae antibodies and immunofluorimetry via Luminex^® technology for the evaluation of cytokine levels (TNFα, IFNγ, IL-6 and IL-17). The comparison between allelic and genotypic frequencies was performed using the χ² test and the exact Fischer test. The odds ratio (OR) was noted adopting confidence interval of 95%. The comparison between the averages was carried out by the Mann-Whitney and Kruskal-Wallis tests. A factorial discriminant analysis and a binary logistic regression were performed as further analyses. The T300A variant showed an increased risk of CD within homozygous variant carriers (P=0.027). Moreover, the carriage of the G allele was associated with the early onset of CD (P=0.01) and a severe CD impairment (P=0.045). We were not able to comfort the association of the T300A variant and ASCA IgA, ASCA IgG and IFNγ levels detected at the univariate analysis. Our results suggest a possible association between the T300A variant and CD in this cohort of Algerian CD patients. Moreover, this variant might be incriminated in the early onset of CD and a severe disease impairment. At the serological study, the univariate and the multivariate analyses yielded contradictory results. Further investigations of larger cohorts of Algerian CD are needed to better assess the suggested associations at the present study.