Background: Cognitive deficit is a fundamental trait of schizophrenia, but its mecwhanisms remain unknown. The neuregulin 3 (NRG3) gene, involving in neuronal function, has been considered to be associated with schizophrenia and cognition. However, no study has investigated the effects of NRG3 polymorphism on cognitive deficits in a large sample of the patients with schizophrenia. Methods: A total of 1112 schizophrenia patients and 423 controls were recruited and genotyped with NRG3 rs10748842. Among them, 864 patients and 403 controls were assessed for cognition through the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). SHEsis was applied and followed by logistic regression analysis. The models of analyses of covariance (ANCOVA) were constructed to examine the effects of NRG3 rs10748842 on cognitive deficits. Results: No differences in NRG3 rs10748842 allele and genotype were found between patients and controls (both p> 0.05). With the exception of Visuospatial/construction, the other RBANS scores were significantly lower in patients compared to controls after adjusting for gender and education (all p < 0.001). Interestingly, we found that NRG3 rs10748842 was associated with cognitive deficit in schizophrenia, showing that patients carrying C allele had lower attention and total scores than those with TT genotype (both p <0.05). Conclusion: NRG3 rs10748842 may not confer susceptibility to schizophrenia, but may be more closely associated with cognitive deficit, especially attention performance in chronic schizophrenia. (C) 2019 Elsevier B.V. All rights reserved.