Schizophrenia (SCZ), is considered as one of the most debilitating mental disorders around the world. Symptom-based clinical interview and numerous tests have been used to evaluate the diagnosis and also cognitive disturbances in patients with SCZ. All these tests measure phenotype-based functions. Thus, it seems accurate diagnosis of such complex disorders must rely on more valid and reliable factors. In this study, we evaluated the association of transcription factor 4 (TCF4) gene mRNA level in peripheral blood with SCZ, and also its psychopathology, cognitive and intellectual impairments. In this study, using real-time PCR, we compared TCF4 mRNA level between the case (70 unmedicated schizophrenia patients) and healthy control (n = 72) groups. In addition, all subjects underwent Psychopathology (PANSS) and cognitive and intelligence (WAIS, WMS, Stroop, WCST) assessments, and scores were compared between the two groups. Also, to determine the effect of TCF4 expression on psychopathology, cognitive and intellectual functions, the correlation between expression level and test scores was measured. The correlation between gene expression and age of onset and duration of the disorder was evaluated as well. Our results showed that the TCF4 mRNA level, psychopathology, cognitive and intellectual functions were significantly different in all, male, and female patients compared to healthy participants. Additionally, it was found that TCF4 level is positively correlated with scores of WAIS and WMS and is negatively correlated with Stroop and WCST errors and PANSS score. Our results showed that the mRNA level of TCF4 may be associated with SCZ, its psychopathology, IQ and cognitive impairments in an Iranian group of patients with SCZ. These results may help to better understanding the TCF4 role in the psychopathogenesis of SCZ and also may shed some light on the ongoing works conducted on peripheral biomarker-based diagnosis of complicated mental disorders.