Schizophrenia is a chronic and disabling disease of the brain. Schizophrenic patients have auditory hallucinations, delusions and reduced social skills. Recent studies suggest that the genetic polymorphisms are linked with development of schizophrenia. Polymorphisms of schizophrenia susceptibility and different cytokine genes act as the genetic markers. The objective of our study is to examine the association between the neuregulin 1 and tumor necrosis factor-α (-308) gene polymorphism with schizophrenia. This association was performed on the basis of molecular biology to screen the mutations of neuregulin 1 and tumor necrosis factor-α (-308) gene in schizophrenic patients by polymorphism analysis. Statistical analysis of the observed data shows that there was an association (P = 0.003) between patient's group and controls in terms of genotypes of single-nucleotide polymorphism 1 rather than single-nucleotide polymorphism 2 of neuregulin 1. So, heterozygous (adenine/guanine) allelic pattern can be a higher risk factor of schizophrenic patients. Polymorphism of tumor necrosis factor-α (-308) gene indicated frequent presence of homozygous (adenine/adenine) allelic pattern in patient's group than in controls (P = 0.015). Statistical analysis indicates that the age distribution has significant difference between patient's group and controls (P = 0.022) while the gender ratio is not significantly different (P = 0.366) between the two groups. It was concluded that in Pakistani population the neuregulin 1 and tumor necrosis factor-α (-308) genes are strongly associated with schizophrenia.