C8orf4, thyroid cancer-1 (TC1), was first identified in papillary thyroid carcinoma and encodes a nucleus-localized protein. A recent array-based study implicated the presence of copy-number variations (CNVs) of C8orf4 in the genomes of acute myelogenous leukemia. However, the functional impact of such regions needs to be extensively investigated in large amount of clinical samples. The purpose of this study is to confirm the relationship between C8orf4 CNVs and hematological malignancies. In our study, we collected bone marrow samples from 515 hematological malignancies and 102 healthy controls. And the CNVs of C8orf4 were detected by real-time PCR. We found significant association between the copy-number deletions of C8orf4 and the risk of these hematological malignancies including acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), multiple myeloma (MM), and myelodysplastic syndrome (MDS). We also found that the expression of C8orf4 mRNA was relatively lower in the samples with 1 copy of DNA than those with 2 copies of DNA. The CNVs of C8orf4 were associated with the risk of hematological malignancies.