Psychiatric disorders are neurotransmitter function disorders in the brain that lead to cognitive, emotional or behavioral dysfunction. In the world, over 80 million people suffer from mental illness, and each year the number of patients is increasing. Their development is influenced by genetic factors, environmental factors and chronic stress. Psychiatric disorders cause everyday subjective suffering and reduce work ability, quality of life of a patient, but also his / her environment. Methylentetrahydrofolate reductase (MTHFR) is an enzyme that plays a significant role in the metabolism of folate and methylation of DNA, which it affects the synthesis of neurotransmitters. Changed folate metabolism is a pathophysiological basis for the development of mental illness. One of the causes of the changed metabolism of folate is reduced activity of the MTHFR enzyme as a consequence of gene polymorphism. The most significant MTHFR mutations associated with the development of psychiatric diseases are C677T and A1298C. This study was conducted on 155 hospitalized patients of the Psychiatric Hospital "Sveti Ivan" in Zagreb and 101 healthy volunteer blood donors to examine the correlation of MTHFR C677T and A1298C mutations with the development of mental illnesses in Croatian population. All subjects was taken a peripheral blood sample with K₂EDTA anticoagulant with informed consent. DNA isolation with a commercial test kit QIAamp DNA Blood mini QIAcube kit (Qiagen GmbH, Hilden, Germany) on the QIAcube device was performed and MTHFR mutation genotypes were detected by real-time chain reaction polymerase and allelic discrimination. Results were subjected to statistical comparison by χ2-test, odds ratio (OR) with 95 % confidence interval (CI) and with proportial difference test. There was no statistically significant difference in the occurrence of individual genotypes and alleles in patients with mental illness and control group, C677T mutation (OR 1.04, 95 % CI 0.628-1.727), A1298C mutation (OR 1.002, 95 % CI 0.605 -1.658). The results of this study did not demonstrate the correlation of both MTHFR mutations with the occurrence of mental illnesses on the examined sample of the Croatian population.