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Objective Calculating the abundance of proteins by the peptides is an important part of proteomics.The abundance of degenerate peptides may be due to the contributions from multiple proteins, and removing the degenerate peptides directly can eliminate the uncertainty and simplify the problem.However, because the information of the degenerate peptides is not fully utilized, the accuracy of the protein abundance may be affected and the amount of protein that can be quantified may significantly be reduced.How to make full use of the information of degenerate peptides to improve the accuracy and comprehensiveness of protein quantification, and not lead to more complex problems, is an important issue.Methods We provide a method based on error-minimization-based quantification for protein (EMQ) .Unlike most of the previous algorithms, EMQ takes advantage of the information in the degenerate peptides to maximize the reduction of peptide level information to the protein level, obtaining more protein quantitative results and improving the accuracy.Results The results in multiple experimental data show that our method can get higher accuracy and more protein quantification results with a relatively short time.Conclusions The method based on error minimization proposed in this paper can quickly and accurately be applied in large-scale proteomics problems.