Krüppel-like factors (KLFs, total 18 members) from the zinc finger protein (ZFP) super-family have a wide range of biological functions in hepatocellular carcinoma (HCC). This paper reviews the recent some progresses of aberrant KLFs with their potential values for diagnosis, prognosis, and targeted therapy in HCC. The recent advances of oncogenic KLFs in the diagnosis, prognosis, and targeted therapy of HCC were reviewed based on the related literature on PUBMED and clinical investigation. Based on the recent literature, KLFs, according to biological functions in HCC, are divided into 4 subgroups: promoting (KLF5, 7, 8, 13), inhibiting (KLF3, 4, 9~12, 14, 17), dual (KLF2, 6), and unknown functions (KLF1, 15, 16, or 18 ?). HCC-related KLFs regulate downstream gene transcription during hepatocyte malignant transformation, participating in cell proliferation, apoptosis, invasion, and metastasis. Some KLFs have diagnostic or prognostic value, and other KLFs with inhibiting promoting function or over-expressing inhibiting roles might be molecular targets for HCC therapy. These data have suggested that Abnormal expressions of KLFs were associated with HCC progression. Among them, some KLFs have revealed the clinical values of diagnosis or prognosis, and other KLFs with the biological functions of promotion or inhibition might be as effectively molecular targets for HCC therapy.