This study aimed to investigate whether plasma levels of HDL cholesterol (HDL-C) were associated with the risk of intracerebral hemorrhage (ICH). Plasma HDL-C was determined via enzymatic methods, and ICH was ascertained via medical history, physical examination, and brain imaging (computed tomography or magnetic resonance imaging). The multivariable logistic regression model was used to calculate the odds ratios (OR) and 95% confidence intervals (CI) of ICH according to levels of plasma cholesterol. A total of 170 patients with ICH were identified from 6,046 participants. After adjustment for conventional cardiovascular risk factors, the OR was 2.06 (95% CI, 1.25-3.12; P < 0.01) for participants in the first tertile of HDL-C levels (<1.38 mmol/l) and 1.13 (95% CI, 0.72-1.78; P = 0.59) for participants in the second tertile (1.38-1.64 mmol/l), compared with participants in the third tertile (∩≥1.65 mmol/l). Subgroup analysis indicated that the detrimental effects of HDL-C were more significant in men and lean participants than in their corresponding controls, independent of hypertension. The results presented herein indicate that low plasma HDL-C (<1.38 mmol/l) may be associated with risk of ICH.