Hepatitis C infection is a major health problem worldwide, especially in Egypt. The high prevalence of mixed cryoglobulinemia (MC) in hepatitis C patients leads to the assumption that there is a direct link between hepatitis C virus (HCV) and cryoglobulinemia. Host genetic factors could be a contributing factor. B cell-activating factor (BAFF) is a tumor necrosis factor (TNF) family member, which has an essential role in B lymphocyte development and survival. The aim of the present work was to study the possible association between the BAFF -871C/T promoter polymorphism and HCV-related MC in a cohort of Egyptian patients.The study was conducted in 120 HCV patients classified into two groups: group I (60 HCV patients with MC) and group II (60 HCV patients without MC), with 60 age- and sex-matched healthy control subjects. BAFF -871C/T genotyping was performed in all subjects by polymerase chain reaction (PCR) with restriction fragment length polymorphism analysis.The prevalence of the BAFF -871TT genotype was significantly increased in HCV patients compared with the control group (P=0.036). The BAFF TT genotype was also significantly more prevalent in group I (HCV-MC patients) than in group II (HCV patients without MC) [P<0.001].A significant association was found between the BAFF -871C/T promoter polymorphism and MC, which may indicate that BAFF could be a potential therapeutic target in HCV-MC.