The Genotype-Tissue Expression (GTEx) resource has provided insights into the regulatory impact of genetic variation on gene expression across human tissues; however, thus far has not considered how variation acts at the resolution of the different cell types. Here, using gene expression signatures obtained from mouse cell types, we deconvolute bulk RNA-seq samples from 28 GTEx tissues to quantify cellular composition, which reveals striking heterogeneity across these samples. Conducting eQTL analyses for GTEx liver and skin samples using cell composition estimates as interaction terms, we identify thousands of genetic associations that are cell-type-associated. The skin cell-type associated eQTLs colocalize with skin diseases, indicating that variants which influence gene expression in distinct skin cell types play important roles in traits and disease. Our study provides a framework to estimate the cellular composition of GTEx tissues enabling the functional characterization of human genetic variation that impacts gene expression in cell-type-specific manners.