Objective To investigate the effect of the interaction between serum S100β protein and brain-derived neurotrophic factor （BDNF）-rs6265 gene polymorphism on the efficacy of nerve block in the treatment of dysphagia after ischemic stroke.Methods After nerve block therapy， 285 patients with dysphagia after ischemic stroke were divided into two groups effective group with 226 patients and ineffective group with 59 patients according to the evaluation criteria of the water swallow test. The two groups were compared in terms of the serum levels of S100β protein and BDNF and the genotype and allele frequencies of BDNF-rs6265. The association between BDNF-rs6265 gene polymorphism and ineffective treatment was analyzed， and clinical features were compared between the patients with different genotypes. The multivariate logistic regression analysis was used to investigate the risk factors for ineffective nerve block therapy.Results There were significant differences between the two groups in age， NIHSS score， modified Barthel Index， the serum levels of S100β protein and BDNF， and BDNF-rs6265 genotype （P<0.05）. After adjustment for confounding variables， the risk of ineffective treatment in CC genotype carriers was 1.762 times that in patients with TT genotype， and there were significant differences in drinking history， hypertension， NIHSS score， serum S100β protein， and BDNF between the patients with CC， CT and TT genotypes （P<0.05）. Serum S100β protein ≥0.44 pg/mL， BDNF <6.21 ng/mL， and BDNF-rs6265 carrying C allele were risk factors for ineffective nerve block therapy （P<0.05）. Both serum S100β protein and BDNF had interaction with BDNF-rs6265 gene polymorphism. The risk of ineffective nerve block therapy in the group with abnormal serum levels of S100β protein and BDNF and BDNF-rs6265 gene polymorphism was 2.77 times that in the group with no such conditions.Conclusions Serum S100β protein level and BDNF-rs6265 gene polymorphism are associated with the efficacy of nerve block therapy in patients with dysphagia after ischemic stroke， with interaction between the two indicators.