Objectives: Postoperative cognitive dysfunction (POCD) is objectively measurable after anesthesia and surgery. Lower heart rate variability (HRV) is associated with poorer cognitive performance, but the relationship between HRV and POCD remains unclear. Methods: Elderly patients who underwent total hip replacement under general anesthesia from the Department of Bone and Joint Surgery, Affiliated Hospital of Southwest Medical University were enrolled. Neuropsychological tests, standard deviation of the interbeat interval (SDNN, a parameter of HRV), and plasma concentrations of glial cell line-derived neurotrophic factors (GDNF) were performed one day before (T-1) and 7 days after (T7) surgery. Results: POCD occurred in 35% of patients on 7 days after surgery. Lower SDNN(T7) (OR=.91) and longer surgery time (OR=1.33) were associated with POCD. Compared with patients without POCD, there was higher variation SDNN (Δ SDNN) and plasma GDNF (ΔGDNF) in those with POCD from T-1 to T7 period. ΔGDNF is positively correlated with ΔSDNN (r = .61, p<.001). Conclusions: Lower SDNN (T7) was associated with POCD and might be used as a warning indicator for the risk of POCD.