The complement protein C3a is a key component of the innate immune system.  We utilised a murine model of melanoma (B16-F0) to identify a hitherto unknown role for C3a-C3a receptor (C3aR) signalling in promoting tumour growth.  The development and growth of B16-F0 melanomas was retarded in mice lacking C3aR, while growth of established melanomas was arrested by C3aR antagonism.  Flow cytometric analysis showed alterations in tumour-infiltrating leukocytes in the absence of C3aR.  Specifically, neutrophils and CD4⁺ T lymphocyte sub-populations were increased, whereas macrophages were reduced.  The central role of neutrophils was confirmed by depletion experiments which reversed the tumour inhibitory effects observed in C3aR-deficient mice, and returned tumour infiltrating CD4⁺ T cells to control levels.  Analysis of the tumour microenvironment showed up-regulation of inflammatory genes which may contribute to the enhanced anti-tumour response observed in C3aR-deficient mice.  C3aR deficiency/inhibition was also protective in murine models of BRAF^V600E mutant melanoma, colon and breast cancer, suggesting a tumour-promoting role for C3aR signalling in a range of tumour types.  We propose that C3aR activation alters the tumour inflammatory milieu, thereby promoting tumour growth.  Therapeutic inhibition of C3aR may therefore be an effective means to trigger an anti-tumour response in melanoma and other cancers.