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Aims: Herein, we examined the correlation between platelet/high-density lipoprotein cholesterol ratio (PHR) and symptoms of depression among United States adults. Methods: Data acquired from the 2007–2018 National Health and Nutrition Examination Survey, involving individuals ≥ 20 years of age, with available PHR and depression diagnosis information. We employed weighted uni- and multivariable logistic regression analyses to assess the distinct correlation between PHR and depressive symptoms. Additionally, we conducted subgroup, interaction, and restricted cubic spline analyses. Results: In all, 28,098 subjects were recruited for analysis, with 8.04% depression status and 19.31 ± 0.11 mean PHR value. Depressive symptoms increased with higher quartiles of PHR. Following fully confounder adjustments in model 2, participants with the largest PHR quartiles exhibited a 53% (OR: 1.53, 95%CI: 1.00–2.33, P = 0.05) raised depressive symptoms, relative to participants with least PHR quartiles. Based on the two-piece-wise regression, the breakpoint was PHR = 23.76, and a positive association was more evident when PHR < 23.76 (OR = 1.06, 95%CI: 1.02–1.10, P = 0.01). When PHR ≥ 23.76, the correlation disappeared (P = 0.85). Using subgroup and interaction analyses, we revealed a positive relationship between PHR and depressive symptoms almost consistent among various population settings. Conclusions: A convenient biomarker, the PHR was independently associated with an increased risk of depressive symptoms and may be a promising new bioindicator for the prediction of depression diagnosis. [ABSTRACT FROM AUTHOR]