For historical reasons, most proteomics workflows focus on MS/MS identification, but consider quantification as the end point of a comparative study. The stochastic data-dependent MS/MS acquisition (DDA) gives low reproducibility of peptide identifications from one run to another, which inevitably results in problems with missing values when quantifying the same peptide across a series of label-free experiments. However, the signal from the molecular ion is almost always present among the MS1 spectra. Contrary to what frequently being claimed, missing values do not have to be an intrinsic problem of DDA approaches that perform quantification at the MS1 level. The challenge is to perform sound peptide identity propagation across multiple high-resolution LC-MS/MS experiments, from runs with MS/MS-based identifications to runs where such information is absent. Here we present a new analytical workflow DeMix-Q (https://github.com/userbz/DeMix-Q), which performs such propagation that recovers missing values reliably by using a novel scoring scheme for quality control. Compared to traditional workflows for DDA as well as previous DIA studies, DeMix-Q achieves deeper proteome coverage, fewer missing values and lower quantification variance on a benchmark dataset. This quantification-centered workflow also enables flexible and robust proteome characterization based on covariation of peptide abundances.