Tumor Necrosis Factor α (TNF) plays a dual, still enigmatic role in melanoma, either acting as a cytotoxic cytokine or favoring a tumorigenic inflammatory microenvironment. Herein, the tumor growth of melanoma cell lines expressing major histocompatibility complex class I molecules at high levels (MHC-Ihigh) was dramatically impaired in TNF-deficient mice and this was associated with enhanced tumor-infiltrating CD8+ T lymphocytes. Immunodepletion of CD8 T cells fully restored melanoma growth in TNF-/- mice. Systemic administration of Etanercept inhibited MHC-Ihigh melanoma growth in immunocompetent but not in immunodeficient (IFNγ-/-, nude or CD8-/-) mice. MHC-Ihigh melanoma growth was also reduced in mice lacking TNF-R1, but not TNF-R2. TNF-/- and TNF-R1-/- mice as well as Etanercept-treated WT mice displayed enhanced intra-tumor content of high endothelial venules (HEV) surrounded by high CD8+ T cell density. Adoptive transfer of activated TNF-R1-deficient or proficient CD8+ T cells in CD8-deficient mice bearing B16K1 tumors demonstrated that TNF-R1 deficiency facilitates the accumulation of live CD8+ T cells into the tumors. Moreover, in vitro experiments indicated that TNF triggered activated CD8+ T cell death in a TNF-R1-dependent manner, likely limiting the accumulation of tumor-infiltrating CD8+ T cells in TNF/TNF-R1-proficient animals. Collectively, our observations indicate that TNF-R1-dependent TNF signaling impairs tumor-infiltrating CD8+ T cell accumulation and may serve as a putative target to favor CD8+ T cell-dependent immune response in melanoma.