Background: With the advance of experimental technologies, large-scale protein quantification is widely applied to sample analysis in proteomics.Different stable isotope labeling methods have been developed for the comparison of different samples on the mass spectrometry (MS) platforms.Several software tools have been developed for single or multiple labeling techniques.However, there are few software tools available that can support most of the widely used labeling techniques, and has easily accessible graph user interface (GUI) and fairish computation speed.Methods: Here, we present an effective tool for protein quantification based on the stable isotope labeling MS data, which introduces a compact Index MS raw data file (IdxRaw) to accelerate the quantitative information extraction, a least square fitting with nonlinear optimization algorithm for the universal quantitative calculation on single MS spectrum from different isotopic labeling techniques.S/N ratio and R-square of the linear fitting were calculated as filter criteria during the construction of extracted ion chromatogram (XIC).Then, linear regression normalization and Dixons Q-test are applied for combining the peptide ratio in reduplicate runs.A protein ratio was defined as a weighted average of unique peptide ratios.Results: In this tool, batch processing for the large scale data analysis and GUI for the manual inspection and validation are integrated.The user can easily trace the details of protein quantification, including the extracted ion chromatogram (XIC) for each peptide, the paired isotopic peaks in the MS spectrum and several parameters for the result evaluation.The merits of SILVER were verified by applying it to datasets with different isotopic labeling.Conclusions: SILVER shows high accuracy and relative robustness on both the peptide level and the protein level.Whats more, it also includes a user-friendly visualization platform, which permits users to validate the results .