Updated project metadata. Generation of a new library of targeted mass spectrometry assays for accurate protein quantification in malignant and normal kidney tissue. Aliquots of primary tumor tissue lysates from 86 patients with initially localized renal cell carcinoma (RCC), 75 patients with metastatic RCC treated with sunitinib or pazopanib in the first line and 17 adjacent normal tissues treated at Masaryk Memorial Cancer Institute (MMCI) in Brno, Czech Republic, or University Hospital Pilsen (UHP), Czech Republic, were used to generate the spectral library. Two previously published datasets (dataset A and B) and two newly generated RCC datasets (dataset C and D) were analyzed using the newly generated library showing increased number of quantified peptides and proteins, depending on the size of the library and LC-MS/MS instrumentation. This PRIDE project also includes quantitative analysis results for all four datasets and raw files for dataset C and D. Dataset A is characterized in DOI: 10.1038/nm.3807. It consists of 18 samples from 9 RCC patients involving one cancer and non-cancerous sample per patient. Dataset B is characterized in DOI: 10.3390/biomedicines9091145. It consists of 16 tumor samples and 16 adjacent normal tissues from 16 mRCC patients treated at Masaryk Memorial Cancer Institute (MMCI) in Brno, Czech Republic. Dataset C involves only tumor tissues from dataset B. Half of them responded to sunitinib treatment in the first line three months after treatment initiation and half did not. Dataset D involves 16 RCC patients treated at University Hospital Pilsen (UHP), Czech Republic. All were localized at the time of initial diagnosis, half of the tumors developed distant metastasis in five years after the diagnosis.