Hallmark pathology associated with the development and progression of cutaneous squamous cell carcinoma includes inflammatory infiltrate and the accumulation of mast cells within the stroma. However, it is still unclear whether mast cell function at the peri-tumoural environment is permissive or protective against tumour progression. Mast cells are versatile effector cells with the ability to release a variety mediators, cytokines, and proteases which are stored in the secretory granules and rapidly released following activation. Mouse mast cell protease 4 (mMCP4) is only synthesised by cutaneous mast cells and is the functional homologue to human mast cell chymase. mMCP4 and human mast cell chymase has functions in vasodilation, extracellular matrix remodelling, cytokine activation and degradation. In this study, we investigated a role for mMCP4 in the regulation of tissue remodelling in critical stages of skin carcinogenesis. Using two models of skin carcinogenesis in mouse, we discovered that mMCP4 plays a protective role. In a model of chronic UVB irradiation, mMCP4 was observed to be protective against ear oedema, ulceration, and inflammation. Moreover, mice lacking MCP4 had a higher incidence of in situ squamous cell carcinoma than wild-type control mice. In a model of multi-stage chemical carcinogenesis of the skin, mice lacking mMCP4 exhibited a higher increased incidence of pre-neoplastic papillomas than wild-type control mice. Protease target analysis suggests a role for mMCP4 in cutaneous extracellular matrix homeostasis that protects against skin carcinogenesis. Our data therefore indicates that mMCP4 plays a protective role against cutaneous carcinogenesis, possibly by normalising ECM structure.