Background <p>Hemoglobin glycation index (HGI), a novel metabolic marker, has demonstrated significant associations with adverse clinical outcomes in multiple major diseases. However, the correlation of HGI with mortality in hyperlipidemic populations has rarely been studied. This cohort study sought to elucidate the link of HGI with short-term mortality of critically ill individuals with hyperlipidemia.</p> Methods <p>Data regarding patients diagnosed with hyperlipidemia were retrospectively retrieved from the Medical Information Mart for Intensive Care IV database and stratified into four groups on the basis of the quartiles of continuous HGI. The main endpoints were in-hospital mortality and 28-day mortality. We utilized various statistical.</p> Results <p>An overall of 3,229 participants (57.9% male) with a median age of 71.01 years (IQR: 61.72, 80.63) were included. K-M survival analysis demonstrated that patients with higher HGI were associated with decreased mortality risks (log-rank p &lt; 0.001). Fully adjusted Cox regression analyses indicated that the elevated HGI was independently associated with reduced risks of both in-hospital mortality (HR 0.833, 95% CI 0.763-0.910, p &lt; 0.001) and 28-day mortality (HR 0.858, 95% CI 0.793-0.927, p &lt; 0.001). RCS analyses confirmed linear relationships of ascending HGI with decreased risks regarding in-hospital and 28-day mortality. Additionally, incorporating HGI into existing models improved short-term mortality prediction performance. Subgroup analysis further showed a strong link of HGI with mortality among patients aged ≥ 65 years and those without diabetes.</p> Conclusions <p>The study underscored that a lower HGI was significantly associated with a higher risk of short-term mortality among critically ill patients with hyperlipidemia.</p> Clinical trial number <p>Not applicable.</p>