Cluster of differentiation (CD)151, a member of tetraspanin family, is considered to be the first tetraspanin to be associated with tumor metastasis. Previous studies in vivo, in vitro and in the clinic have demonstrated that CD151 is involved in tumor progression at different levels through interaction with integrins, growth factor receptors and matrix metalloproteinases. Transcatheter arterial chemoembolization (TACE) is widely recommended for the treatment of patients with advanced hepatocellular carcinoma (HCC) worldwide. It has been hypothesized that TACE may create a hypoxic-ischemic environment that increases the expression of tumor progression-associated factors, promotes the angiogenesis of HCC, and initiates the recurrence and metastasis of HCC. Whether TACE promotes HCC progression remains controversial and numerous studies have focused on the influence of TACE on a number of tumor progression-associated factors. In the present study, the expression of serum CD151 in patients with HCC prior to and following TACE and its association with clinicopathological characteristics was investigated. It was revealed that the expression level of CD151 at 5-7 days post-TACE was significantly increased compared with pre-TACE levels. Risk factors and protective factors associated with tumor progression following a single TACE procedure and 18 months of follow-up were also identified. Furthermore, the present study revealed that a pre-TACE CD151 level of >0.3247 ng/ml and a 5-7 days post-TACE CD151 level of >0.3146 ng/ml revealed moderate sensitivity and specificity for predicting HCC progression following a single TACE procedure. The present study highlights CD151 as a useful marker in predicting the response to treatment and monitoring the disease course following TACE.