The aim of this study is to explore whether there is an association between the genotype of serotonin-transporter-linked polymorphic region (5-HTTLPR) and migraine combined with depression. One hundred and sixteen patients with migraine and depressive disorder (Group A) and 116 patients with simple migraine (Group B) admitted in Mental Health Center, Zhejiang University School of Medicine, China, from January 2018 to April 2020 were included in the present study. Polymerase chain reaction (PCR) and restriction fragment length polymorphism techniques were used for detection of 5-HTTLPR genotype. The 5-HTTLPR genotype and allele frequency between the two groups were compared. The results showed that there was no significant difference in 5-HTTLPR genotype (L/L, L/S and S/S) frequency and allele (S and L) frequency between Group A and Group B (p=0.794 and 0.491, respectively). In conclusion, 5-HTTLPR genotype might not be related to the onset of migraine combined with depression. Key Words: Migraine, Depressive disorder, Serotonin-transporter-linked polymorphic region (5-HTTLPR).