Autism is a heterogeneous and multifactorial disease that results from the interaction between genetic vulnerability and environmental factors. Several studies showed that many of genes that play role in autism are component of signaling networks that regulate growth and synaptic plasticity, play an important role in the etiology of autism. Contactin associated-like 2 (CNTNAP2) gene is a member of the superfamily of synaptic adhesion proteins and encodes a scaffold protein called CASPR2 that is involved in the interaction of neuron-glia and clusters K+ channels in myelinated axons. CNTNAP2 is highly expressed during the nervous system development. In this study the association of rs7794745 CNTNAP2 gene polymorphism and autism was investigated. Two hundred patients with autism and 260 healthy individuals were included in this study. Genomic DNA was extracted from peripheral blood cells. Genotypes were analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Statistical analysis was performed using the software MedCalc (12.1). The genotype frequencies of AA, AT, TT were 35.3%, 50.7% and 13.8% in controls and these values were 32% and 68% and 0% in patients with autism, respectively (P=0.0001) (OR=0.01, 95% CI 0.001-0.32). The frequency of A and T alleles were 66%, 34% in patients and 60%, 40% in controls, respectively (P=0.11). The results of this study showed that there is a significant association between rs7794745 CNTNAP2 gene polymorphism and autism in the studied population. However, to obtain a definitive conclusion larger studies with more patients and controls are needed to confirm the results.