Gene expression varies between individuals and corresponds to a key step linking genotypes to phenotypes. Regulation of transcript and protein abundances can affect the final phenotypes and has been related to many human diseases. However, our knowledge regarding the species-wide genetic control of protein abundance, including its dependency on transcript levels, is very limited. Here, we have determined quantitative proteomes of a large population of 942 diverse natural Saccharomyces cerevisiae yeast isolates. We found that mRNA and protein abundances are weakly correlated at the population gene level (r = 0.165). While the protein co-expression network recapitulates the major biological functions, differential expression patterns reveal proteomic signatures related to specific populations, mainly domesticated. Most importantly, comprehensive genetic association analyses highlight that genetic variants associated with variation in protein (pQTL) and transcript (eQTL) levels poorly overlap (3.6%), with mostly common local QTL. Our results demonstrate that transcriptome and proteome are clearly two distinct layers of regulation, governed by distinct genetic bases in natural populations, and therefore highlight the importance of integrating these different levels of gene expression to better understand the genotype-phenotype relationship. This submission contains the raw files for the wild isolates collection, the library used for the analysis and the corresponding DIA-NN report and associated files.