Background: Malnutrition, systemic inflammation, and atherosclerosis known as MIA syndrome occurs in patients who have undergone regular hemodialysis (HD) and can lower their quality of life (QoL). Current study aimed to determine the interrelation of malnutrition and inflammation to QoL. Methods: A cross-sectional analytic study was conducted in our hemodialysis installation. We performed Malnutrition Inflammation Score (MIS) and measure serum IL-6 to determine malnutrition and inflammation conditions in regular HD patients and utilized ‘Kidney Disease Quality of Life-Short Form (KDQOL-SF) to assess QoL MIS. IL-6 cut-off point were determined by the Receiver Operating Curves (ROC) then we performed linear regression to analyze the relationship level of MIS and IL-6 with level of QoL. We also used path analysis to prove the mechanism model of MIS and IL-6 to QoL on regular HD patients. Results: This study consisted of 60 regular HD patients, 40 (66.7%) of men with mean age of 51.8 years and 78 months average of dialysis vintage. Good QoL was obtained ≥60 overall health (above the median value) and high level of MIS was obtained ≥5 with 75% sensitivity and 21.8% specificity, while high IL-6 level were ≥47.21 pg/mL, with 62.2% sensitivity and specificity of 78.3%. This study found the prevalence of protein-energy wasting (PEW) in regular HD patients was 81.7% by using high level of MIS. MIS were significantly correlated to IL-6 (r = 0.376, p = 0.003) however high level of MIS were uncorrelated to poor QoL. The mechanism of the interrelation of MIS, IL-6, and QoL showed on path analysis that MIS was 15% directly correlated to QoL, however, IL-6 indirectly correlated to QoL on regular hemodialysis patients. Conclusion: MIS and IL-6 were correlated to QoL and MIS also correlated to IL-6. Malnutrition inflammatory score directly affected QoL but IL-6 indirectly affected QoL in regular HD patients.