Background As both of peripheral arterial disease (PAD) and depression carried a poor prognosis in patients on maintenance hemodialysis (MHD), we investigated the correlation between the ankle-brachial index (ABI), an indicator of subclinical PAD, and symptoms of depression in patients on MHD. Methods One hundred and twenty-nine patients on MHD (75 males and 54 females, mean age 64.8 ± 12 years) were enrolled in this cross-sectional study, which aimed at evaluating the relationship between symptoms of depression and ABI. Demographic as well as clinical and laboratory variables including status of diabetes, chronic hepatitis C infection, dialysis duration, Charlson comorbidity index (CCI), plasma levels of albumin, C-peptide, insulin, high-sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), adiponectin, and lipid profile were obtained. The self-administered beck depression inventory (BDI) was used to determine the presence or absence of symptoms of depression, and depression was defined as a BDI score ≧14. Multivariable-adjusted linear regression models were constructed to confirm the independent association of biologic parameters of symptoms of depression. Significance was defined as P < 0.05. Statistical analyses were performed using SPSS/Windows software (SPSS Science, v. 15.0, Chicago, IL). Results The mode of multivariate analysis showed that diabetes (β = 3.594; P = 0.040), hepatitis C infection (β = 4.057; P = 0.008), levels of serum albumin (β = −5.656; P = 0.024), C-peptide (β = −0.292; P = 0.002), ABI (β = −9.041; P = 0.031), and Ln-transformed hsCRP were significantly associated with BDI. Conclusions Hepatitis C infection, serum levels of albumin, C-peptide, and ABI levels were found to be correlated with BDI (P < 0.05).