Rationale and Background: : End-stage renal disease (ESRD), also known as end-stage kidney disease, is the final stage of chronic kidney disease, where the kidneys no longer function adequately to support the needs of daily life. The treatments for ESRD are dialysis or kidney transplantation. To assess the health-related quality of life (HQOL) in ESRD patients on hemodialysis at : Objectives: Khammouane Provincial Hospital and Champasak Provincial Hospital, Lao PDR. Methodology: : This descriptive cross-sectional study collected data through questionnaires and face-to-face interviews. The data was collected in Epi-data and analysis was conducted in SPSS using descriptive statistics and exploring associations between HQOL and different participant factors. Results: : A total of 270 participants were included in the study, of whom 68.5% were male. The participants’ ages ranged from 25 to 78 years, with a mean of age was 45.48 years. Hemodialysis (41.1%) had high HQOL; with a mean score of 36/56. More than half the respondents (63.7%) received a high level of family support, while 71.5% received a low level of peer support. Nearly half of participants (41.1%) reported good behavior level. Females were 2.4 times more likely to have high health quality of life compared to male respondents (OR=2.46, 95%CI= 1.18–10.10). It was found that respondents who described themselves as staff/student/merchant were 2.9 times likely to have a high HQOL compared to respondents who were unemployed, a laborer or farmer (OR=2.93, 95%CI= 1.01-8.44). Additionally, ESRD patients who underwent hemodialysis two to three times per week reported a HQOL 3.8 times higher than those who underwent hemodialysis HQOL once per week (OR=3.84, 95% CI=1.30-11.31). The respondents who had a high level of family support were 1.4 times more likely to have a higher HQOL than those who received low levels of family support (OR=1.38, 95% CI=1.48-10.94). Respondents with good health-related behaviours were 2.0 times more likely to have a high HQOL than those with poor behaviours (OR = 3.73, 95% CI: 1.47–9.43). Conclusion: This study found that overall patients with ESRD had a poor health quality of life. Female patients reported higher HQOL than males. More than half of all participants received strong family support but had low levels of peer support. Additionally, health-related behaviours played a significant role in improving HQOL.