Introduction: Human adenovirus 7 (HAdV-7) is an important viral pathogen of severe pneumonia in children and a serious threat to health. Methods: A cohort of 45 pediatric patients diagnosed with HAdV-7-associated severe pneumonia and admitted to the Pediatric Intensive Care Unit at the Children's Hospital of Chongqing Medical University from May 2018 to January 2020 were included. Risk factors of death were analyzed by the Cox proportional risk mode with Clinical data, serum, and nasopharyngeal aspirate adenovirus load, Genome analysis, Olink proteomics, and cytokine profile between dead and surviving patients were also analyzed. Results: A total of 45 children with a median age of 12.0 months (interquartile range [IQR]: 6.5, 22.0) were included (female 14), including 14 (31.1%) who died. High serum viral load was an independent risk factor for mortality (hazard ratio [HR] = 2.16, 95% confidence interval [CI], 1.04-4.49, p = 0.039). BTB and CNC homology 1 (BACH1), interleukin-5 (IL-5), and IL-9 levels were significantly correlated with serum viral load (p = 0.0400, 0.0499, and 0.0290; r = 0.4663, 0.3339, and -0.3700, respectively), with significant differences between the dead and survival groups (p = 0.021, 0.001, and 0.021). Conclusions: Severe cytokine storm-associated high serum viral load after HAdV-7 infection may be the main mechanism responsible for poor prognosis in children.