Dialysis patients typically experience significantly poorer health-related quality of life (HRQOL) compared to the general population. In Libya, hemodialysis (HD) patients face additional burdens, including limited medical care access and the disruptive effects of political instability. Cities such as Derna and Benghazi remain understudied despite the value such data would offer for improving care. This study aimed to assess HRQOL among Libyan HD patients and identify its predictors. Using a cross-sectional design, we recruited participants from two HD facilities, the Derna Kidney Centre and Al-Hawari Kidney Services, from January to June 2020. Overall, HD patients showed diminished HRQOL, with mean scores of 46.59 for the physical component summary (PCS), 47.87 for the mental component summary (MCS), and 54.68 for the kidney disease component summary (KDCS); gender emerged as a meaningful predictor, with female patients consistently scoring lower than males across all domains, including PCS (41.03±17.25, p=0.01), MCS (39.17±18.23, p=0.001), and KDCS (43.79±16.51, p=0.001), while comorbid conditions also mattered, with diabetes mellitus associated with the poorest outcomes across every subscale PCS (32.44±16.20, p=0.013), MCS (29.55±8.69, p=0.043), and KDCS (46.52±13.68, p = 0.031). Libyan patients with end-stage renal disease experience reduced HRQOL, with physical functioning affected more severely than mental well-being or kidney-disease-specific quality of life, and gender and comorbidity, particularly diabetes, were identified as key predictors of HRQOL outcomes among this population.