Objective To investigate the correlation between autonomic nervous system dysfunction and intra-dialytic hypotension (IDH) in maintenance hemodialysis (MHD) patients by analyzing the heart rate variability (HRV). Methods Blood pressure changes were recorded and dynamic electrocardiography (Holter) was conducted in 60 MHD patients during a hemodialysis session. Patients were assigned into IDH group or control group. The difference in power spectra of HRV between the two groups was analyzed. The normalized low-frequency (LFn) component of HRV was assumed to be the index of sympathetic activity, and the normalized high-frequency (HFn) component to be the index of parasympathetic activity. The LF/HF ratio then indirectly represents the balance level between sympathetic and vagal activities. A logistic regression model was set up to analyze the value of LFn for the prediction of IDH, using IDH as the outcome variable, and parameters including sex, age, hemodialysis age, diabetes as the primary disease, cardiac index, central blood volume/body weigh ratio, ultrafiltration volume/body weight ratio and LFn before hemodialysis as the prediction variables. Results In control group, LFn and LF/HF ratio elevated continually and gradually in a dialysis session (The median of LFn was 65.47nu at the beginning of hemodialysis, 73.79nu after 210 minutes, P=0.001; The median of LF/HF ratio was 2.17 at the beginning, and 3.98 after 210 minutes, P＜0.001), whereas HFn reduced gradually (The median of HFn was 30.06nu at the beginning and 19.43nu after 210 minutes, P=0.002). In IDH group, however, the above indexes changed inconsistently, and LFn was lower than that of control group in the entire hemodialysis session. Logistic regression model showed that LFn was a predictor for IDH (OR= 0.943, 95%CI=0.894～0.966) after adjustment by the above demographic characteristics and basic clinical situations. Conclusion In MHD patients, the presence of IDH may relate to the incapability of continuous and consistent increase of sympathetic activity along with blood volume reduction during hemodialysis. Decrease of basal sympathetic activity before hemodialysis is an independent risk factor for IDH, suggesting that abnormal autonomic nervous function is one of the important causes leading to IDH.