Long-term antipsychotic treatment for schizophrenia is associated with the development of tardive dyskinesia (TD), which is involved in increased cognitive impairment. Dopamine beta-hydroxylase (DBH) gene associated with dopamine and norepinephrine systems influences cognition. Schizophrenia with TD have higher DBH activity than those without TD. This study examined whether DBH5′-insertion/deletion (-Ins/Del) polymorphism could influence cognitive function in schizophrenia with and without TD. The presence of DBH5′-Ins/Del polymorphism was determined in 345 schizophrenia with TD and 397 schizophrenia without TD. The Abnormal Involuntary Movement Scale and Repeatable Battery for Assessment of Neuropsychological Status (RBANS) were used to assess TD severity and cognition. The allele and genotype frequencies of DBH5′-Ins/Del polymorphism did not differ between patients with and without TD (both p > 0.05). RBANS total score and subscales did not differ by DBH5′-Ins/Del genotype groups in patients with TD (all p > 0.05). However, attention score significantly differed by DBH5′-Ins/Del genotype groups in those without TD (p < 0.05). Patients without TD who were Del homozygous had significantly lower attention score than those without TD who were Ins alleles (p < 0.05). Immediate memory and attention scores were lower in patients with TD than without TD (both p < 0.05). This study indicated that DBH5′-Ins/Del polymorphism may not play a role in the susceptibility to TD and cognitive deficits in schizophrenia with TD, but it may influence cognitive function in schizophrenia with non-TD. Moreover, schizophrenia with TD experienced greater cognitive deficits than those with non-TD, especially in immediate memory and attention.