Background: Attention deficit hyperactivity disorder (ADHD) is the most frequent pediatric neurodevelopmental disorder. Studies in Mexico about health-related quality of life (QOL) and cognitive characteristics in these patients are scarce. Objectives: The objective of this study is to describe the relationship between cognitive characteristics and health-related QOL in children with ADHD in Puebla, Mexico. Method: A cross-sectional, analytical study was carried out in a second-level care hospital in Puebla, Mexico. Both genders, from 6 to 12 years old patients with ADHD were included. Those with visual/hearing disabilities and/or severe language delays were excluded. Patients who did not complete the information were eliminated. The Wechsler Intelligence Scale for Children IV (WISC-IV), The Neuropsi and Brief Multidimensional Life Satisfaction Scale for Students (as health-related QOL indicator) scales were applied. Spearman test was used; p ≤ 0.05 was considered significant. Results: 104 children were recruited, 71 male (68.26%), medium age was 8.94 years old (SD = 1.83, min = 6, max = 12). Work memory and processing speed (WISC-IV), and memory and attention (Neuropsi) were the most affected domains. Health-related QOL was low at 60%. WISC-IVs intellectual quotient (r = 0.3962, p = 0.000), and Neuropsi's memory and attention (r = 0.451, p = 0.018) reported a significant moderated correlation with health-related QOL. Conclusion: Attention, memory, and processing speed were the most affected cognitive characteristics in children with attention deficit/hyperactivity disorder. Health-related QOL resulted low. Intellectual coefficient, as well as memory and attention, reported a significant moderated correlation with health-related QOL.