Angiogenin was isolated as a tumor angiogenic factor solely on the basis of its angiogenic activity. Its expression is essential for melanoma progression and metastasis. Many studies have mainly focused on how it induces angiogenesis, which allows further melanoma growth and metastasis. Here, we investigated the effects of angiogenin on melanoma cell growth and studied its influence on the expression and function of the basic fibroblast growth factor. We transfected the angiogenin gene in the sense and antisense orientation into A375 cells, and obtained stable angiogenin under-expressing and over-expressing transfectants. We found that in the angiogenin antisense transfectants, the cell proliferation was decreased and the basic fibroblast growth factor-induced cell proliferation was inhibited, but the expression of basic fibroblast growth factor was increased. In contrast, in the angiogenin sense transfectants, the cell proliferation was increased, and the basic fibroblast growth factor-induced cell proliferation was also increased. The expression of basic fibroblast growth factor, however, was decreased. In conclusion, we demonstrated that, besides its angiogenic activity, angiogenin also directly contributes to A375 cell proliferation and is required for the basic fibroblast growth factor to induce cell proliferation. We also demonstrated that the endogenous angiogenin expression levels affect the expression of basic fibroblast growth factor in A375 cells. By targeting angiogenin, therefore, one may find a potential therapeutic approach to human malignant melanoma.