To investigate the potential correlation between lipid accumulation products (LAP) and depression in adults in the United States. We analyzed data from 13,051 participants from the NHANES 2005-2018 cycle. The LAP index was calculated using the waist circumference (WC) and serum triglyceride (TG) levels, which reflect lipid toxicity. Participants who scored ≥10 on the patient health questionnaire-9 (PHQ-9) were considered depressed. Multivariate logistic regression analyses were conducted to explore the association between the LAP index and depression. Furthermore, we conducted subgroup analysis to identify potentially sensitive populations. Smoothed curve fitting and generalized additive model (GAM) regression were performed to verify the association between the LAP index and depression. A total of 13,051 participants were eligible for analysis. After adjusting for all potential confounders, the risk of depression tended to increase with an increasing LAP index (odds ratio [OR]: 1.0011, 95% confidence interval [CI]: 1.0001, 1.0021). Compared to participants with LAP quartile 1, participants with LAP quartile 3 exhibited the highest risk of depression (OR: 1.43, 95%CI: 1.03, 1.99). Subgroup analysis demonstrated a strong association between the LAP index and depression in men (OR: 1.002, 95%CI: 1.001, 1.004) or those with hypertension (OR: 1.002, 95%CI: 1.000, 1.003). Additionally, smoothed curve fitting and GAM regression demonstrated a positive linear correlation between the LAP index and depression. Our findings suggest that individuals with a higher LAP index may be at higher risk of depression, particularly men or those with hypertension. However, further studies are required to confirm these findings.