This study investigated the relationships between HDL-C and major types of blood cancers. Competing risks regression was used to examine the hazard ratios of hematologic malignancies in 9,596,145 individuals (≥20 years) using data from the Korean National Health Insurance Service (2009-2017). The incidence of the following hematologic cancers was determined based on the International Classification of Diseases 10th revision: Multiple Myeloma (MM), Hodgkin Lymphoma (HL), Non-Hodgkin Lymphoma (NHL), Lymphoid Leukemia (LL), and Myeloid Leukemia (ML). During an average of 8.3 years of follow-up (79,179,225 person-years), 15,864 incident hematologic malignancies were identified. Compared to those in the highest HDL-C quartile, subjects in the lowest HDL-C quartile had the highest risk of all hematologic cancers combined (adjusted hazard ratio [HR], 95% confidence interval [95% CI] = 1.31, 1.25-1.37) and of each respective type of blood cancer, as follows: MM (HR 1.61, 95% CI, 1.46-1.76), HL (HR 1.35, 95% CI 1.07-1.70), NHL (HR 1.12, 95%CI 1.04-1.21), LL (HR 1.36, 95% CI 1.16-1.61), and ML (HR 1.33, 95% CI 1.22-1.45). Low HDL-C level was significantly associated with increased risk of hematologic malignancy, suggesting that a low HDL-C level is an independent risk factor and preclinical marker for hematologic malignancy.