Background <p>Growing evidence supports the prognostic utility of AISI in adults, but its association with mortality in the critically ill pediatric population remains poorly characterized.</p> Objective <p>To investigate the association between AISI and 28-day all-cause mortality in critically ill pediatric patients.</p> Methods <p>A total of 8,797 patients admitted to the pediatric intensive care unit were included from the PIC Database. The AISI was log₂-transformed and categorized into four groups based on quartiles. The outcomes included 28-day all-cause mortality, both in-hospital and in-ICU. Cox proportional hazards regression, restricted cubic spline, two-piecewise threshold model, and subgroup analyses were used to evaluate the association between AISI and 28-day all-cause mortality.</p> Results <p>Males accounted for 4,930 (56.0%) of the patients. The overall 28-day in-hospital and ICU all-cause mortality rates were 4.3% and 4.2%, respectively. The RCS analysis revealed a significant nonlinear association between the log₂-transformed AISI and both mortality outcomes. Threshold effect analysis identified that the threshold points of log₂-AISI were 5.410 and 5.407 for 28-day in-hospital and ICU mortality, respectively. Subgroup analyses revealed no notable differences between specific patient subgroups.</p> Conclusions <p>This study suggests a nonlinear association between AISI and 28-day mortality in critically ill pediatric patients. AISI levels above the threshold were independently associated with an increased mortality risk.</p>