Recently, a gene named TOSO was identified as being overexpressed and associated with the anti-apoptotic characteristic of chronic lymphocytic leukemia (CLL). However, the association of TOSO expression with clinical features of CLL has not been fully described, especially in Chinese patients. TOSO expression was detected by quantitative RT-PCR in CD19+ sorted cells in a cohort of 81 untreated patients with CLL. The results showed that the expression of TOSO in CLL was significantly higher than that in healthy controls (p = 0.027) and other B-cell lymphoproliferative diseases (p = 0.033). The expression level of TOSO was significantly correlated with Binet staging, IGVH mutation status, age, and time to treatment in CLL. A negative correlation was observed between age and TOSO expression (Spearman's, p = 0.025). No correlation was observed between the expression of TOSO and CD38 or ZAP-70. Cox regression analysis indicated that high expression of TOSO (more than 8.4) was an independent indicator for shorter treatment-free survival in CLL. We conclude that TOSO is specifically overexpressed and associated with progressive disease, and might be an important prognostic factor in CLL.