Objective To explore the risk factors for intradialytic hypotension (IDH) from the perspective of lipid metabolism, so as to provide a new basis for the prevention and treatment of hypotension during dialysis. Methods Patients undergoing maintenance hemodialysis at the Blood Purification Center of Maoming People's Hospital from September 2023 to September 2025 were retrospectively enrolled, and clinical data, laboratory test results, and cardiac ultrasound results were collected. IDH was defined as a decrease in systolic blood pressure ≥20 mmHg or a decrease in mean arterial pressure ≥10 mmHg during dialysis, accompanied by symptoms of hypotension requiring nurse intervention (such as drowsiness, lethargy, dizziness, and muscle cramps), occurring ≥1 time per month. Non-IDH group: frequency of intradialytic hypotension ＜1/10 within 3 months; IDH group: at least one hypotensive event per month within 3 months, with frequency of intradialytic hypotension ≥1/10. Pearson or Spearman analysis was used to analyze factors related to apolipoprotein A1 (apoA1) and high-density lipoprotein-cholesterol (HDL-C), and binary logistic regression was used to analyze the risk factors for IDH.  Results  A total of 216 patients were included in this study, with 120 in the non-IDH group and 96 (44.4%) in the IDH group. The levels of HDL-C (t=5.203, P＜0.001) and apoA1 (t=5.571, P＜0.001) in the IDH group were lower than those in the non-IDH group. ApoA1 was negatively correlated with triglycerides (r=-0.262, P＜0.001), C-reactive protein (r=-0.227, P=0.002), white blood cell count (r=-0.274, P=0.016), and neutrophil count (r=-0.270, P=0.018), and positively correlated with total cholesterol (r=0.294, P＜0.001) and apolipoprotein E (r=0.177, P=0.009); HDL-C was negatively correlated with triglycerides (r=-0.538, P＜0.001), C-reactive protein (r=-0.150, P=0.044), white blood cell count (r=-0.193, P=0.005), and neutrophil count (r=-0.192, P=0.005), and positively correlated with total cholesterol (r=0.159, P=0.020). ROC curve analysis was used to assess the accuracy of apoA1 and HDL-C in predicting IDH. The area under the curve for apoA1 was 0.717 (95% CI: 0.648～0.787, P＜0.001), and the area under the curve for HDL-C was 0.686 (95% CI: 0.615～0.756, P＜0.001). The optimal cut-off value for apoA1 was 1.005, and the cut-off value for HDL-C was 1.185. The binary logistic regression model after multivariate adjustment (adjustment factors included age, sex, body mass index, history of hypertension, history of diabetes, dialysis vintage, ultrafiltration rate, pre-dialysis antihypertensive drugs, albumin, serum prealbumin, hemoglobin, serum creatinine, cardiac ejection fraction, pre-dialysis systolic blood pressure, and diastolic blood pressure) showed that low levels of apoA1 (OR=0.012, 95% CI: 0.001～0.125, P=0.001) and HDL-C (OR=0.050, 95% CI: 0.008～0.319, P=0.002) remained risk factors for IDH.  Conclusion This study found that low levels of apoA1 and HDL-C are independent risk factors for IDH, and apoA1 and HDL-C  have potential protective effects against IDH.