Natural killer (NK) cells are the most frequent circulating innate lymphocytes and play a major role in immunosurveillance against tumour initiation and metastases. The signals and checkpoints that regulate NK cell fitness and function in the tumour microenvironment are not well defined. While the cytokine-inducible SH2-containing protein (CIS) and transforming growth factor (TGF)-b are recognised suppressors of NK cell function by inhibiting IL-15 dependent signalling events and inducing cellular transdifferentiation, the role of other SMAD signalling pathways and TGF-b superfamily ligands in NK cells are unknown. Here we report that NK cells express the type I Activin receptor, ALK4, which upon binding its ligand Activin-A, induces phosphorylation of SMAD2/3 to efficiently suppress NK cell metabolism in response to IL-15. Activin-A impairs human and mouse NK cell growth and downregulates intracellular granzyme B levels to impair tumour killing. Consistent with TGF-b–related effects in NK cells, Activin-A induces NK cells to upregulate several innate lymphoid cell (ILC)1-like markers including CD69, TRAIL and CD49a. This is also true for TGF-b receptor deficient NK cells thus highlighting the independence of the Activin and TGF-b pathways. Finally, therapeutic inhibition of Activin-A by Follistatin significantly slowed orthotopic melanoma growth in mice. We therefore conclude that independent biological pathways target NK cell fitness and function via SMAD2/3 signalling and that therapeutic intervention promotes tumour immunity.