Updated project metadata. Cutaneous squamous cell carcinoma (cSCC) is the most prominent tumor of non-melanoma skin cancers and the most aggressive tumor among keratinocyte carcinoma of the skin, showing a high potential for local invasion and metastasis. The cSCC incidences increased dramatically in recent years and the disease occurs more commonly than any other malignancy. The secretome of cancer cells is currently the focus of many studies in order to identify new marker proteins for different types of cancer and to investigate its influence on the tumor microenvironment. In our study we evaluated whether the secretome of cSCC cells has an impact on keratinocytes, the surrounding tissue cells of cSCC. Therefore, we analyzed and compared the secretome of human A431 cancer cells and of HaCaT keratinocytes by mass spectrometry.