Objective This study aims to investigate the potential correlation between the rs1187929 polymorphism of tyrosine kinase B gene and post-stroke depression (PSD). Methods A total of 78 depression patients (PSD) and 112 non-depression patient controls (NPSD patients) were included in the study. All participants were evaluated using the Hamilton Rating Scale for Depression (HAMD) and further divided into PSD and NPSD groups. PSD patients were diagnosed in accordance with DSM-V criteria. The rs1187929 polymorphism of TrkB was genotyped by using PCR product purification and Sanger double termination sequencing. Results The total prevalence rate was 41.05% . The prevalence rate was 42.86% in men and 38.82% in women ( 字2=0.316,P=0.57). The CC, CT and TT frequencies of PSD group were 26.92% , 48.72% and 24.36% respectively. The CC, CT and TT frequencies of NPSD group were 42.86%, 45.54% and 11.61% respectively. Based on the CC genotype, the relative risk of homozygous mutant TT was 3.341 (字2=7.347, P=0.007, OR=3.341),and the T allele frequency in the PSD group was 48.72% which was higher than 34.38% in the NPSD group. The relative risk of allele T relative to allele C was 1.814 (字2=7.798, P=0.005, OR=1.814). Homozygous mutant TT and allele T were risk factors for post-stroke depression (P<0.05). Conclusion There is a correlation between rs1778929 gene polymorphism and PSD in Han population in South Anhui Province, which warrants further large-scale studies.