Objective <p>The intersection of economics and quality of life in hemodialysis patients with chronic kidney disease–End-stage renal disease is complex. Hemodialysis is a life-saving treatment for patients with end-stage kidney disease, but it is also a very expensive treatment and has a considerable influence on a patient's quality of life, both physically and emotionally. This study aims to predict the cost of illness and quality of life in maintenance dialysis patients in a rural area of South India.</p> Methods <p>Individuals from tertiary care hospitals (N = 55) were filtered to satisfy the study inclusion criteria. We used the cost of illness as a predictor to analyse patients’ direct cost, indirect cost and intangible cost using the Kidney Disease Quality of Life 36 for a period of 6&#xa0;months. Costs were estimated in terms of Indian national rupees (INR; 1 USD ~ INR82.52).</p> Results <p>In our study, 76.3% of patients underwent haemodialysis thrice a week. A total of 52.7% of patients spent INR 100–200 (USD 1.20–2.40) on laboratory investigations monthly. Additionally, 47.2% of patients lost wages between INR 1000–3000 (USD 12–36) per visit, and 52.7% of patient caregivers lost less than INR 3000 (USD 36) due to this procedure. The Kidney Disease Quality of Life-36 analysis revealed a significant impact (p &lt; 0.05) on physical and mental functioning, the burden of kidney disease, symptoms, and the effects of kidney disease on daily life in haemodialysis patients.</p> Conclusion <p>The cost of maintenance haemodialysis like the direct, indirect, and intangible costs significantly burdens patients and caregivers, highlighting the need for additional support and care, particularly those from lower socioeconomic backgrounds in rural areas. This study emphasizes the need for improved access to hemodialysis treatment and support services for critical review.</p>