Background: Patients on hemodialysis universally experience detriments in their general quality of life (QOL). Sense of coherence (SOC) is a long-standing factor that affects QOL. Nevertheless, the association between SOC and QOL in patients on hemodialysis was seldom investigated. Our research aims to study this association in a sample of Leba- nese adult patients on hemodialysis. Methods: In this cross-sectional study, SOC was measured using the short version of the “Orientation of Life" scale (SOC-13). QOL was assessed using the Kidney Disease Quality of Life- Short Form (KDQOL-SF). The association between SOC and QOL and its submodalities was first explored using Pearson Correlation and multivariate linear regression analyses, controlling for sociodemographic variables and medical variables. Results: 157 patients on hemodialysis (mean(SD) age: 62.1(13.81) years; 58.6% males) were included. Mean QOL score was 51.65 and that of SOC was 48.06. SOC was strongly corrected with the total QOL (r = 0.832; p value < 0.001), as well as its physical functioning (r = 0.767; p value < 0.001), emotional functioning (r = 0.757; p value < 0.001), cogni- tive functioning (r = 0.740; p value < 0.001), and social functioning (r = 0.773; p value < 0.001) submodailties. SOC was moderately correlated with professional functioning submodality of QOL (r = 0.618; p value < 0.001), but not cor- related with the satisfaction with the quality of care (r = 0.052; p = 0.520). Within the regression models accounting for sociodemographic and medical variables, SOC was significantly associated with the total QOL (unstandardized B = 0.803; 95% CI 0.714, 0.893), physical functioning (unstandardized B = 0.761; standardized B = 0.763; 95% CI 0.661, 0.861), emotional functioning (unstandardized B = 1.205; standardized B = 0.757; 95% CI 1.037, 1.372), professional functioning (unstandardized B = 1.142; standardized B = 0.498; 95% CI 0.843, 1.442), cognitive functioning (unstand- ardized B = 1.239; standardized B = 0.739; 95% CI 1.058, 1.420), and social functioning (unstandardized B = 0.912; standardized B = 0.768; 95% CI 0.790, 1.034). Conclusions: In a sample of adult patients on hemodialysis, SOC was positively significantly associated with QOL and its submodalities, expect the satisfaction with the quality of care. The confirmation of the general hypothesis that relates the SOC with the QOL encourages more salutogenic research among this patient population.