A hairpin DNA (hpDNA) piezoelectric gas sensors array with heptamer loops as sensing elements was designed, realized, and challenged with pure volatile organic compounds VOCs and real samples (beer). The virtual binding versus five chemical classes (alcohols, aldehydes, esters, hydrocarbons, and ketones) of the entire combinatorial library of heptamer loops (16,384 elements) was studied by molecular modelling. Six heptamer loops, having the largest variance in binding the chemical classes, were selected to build the array. The six gas sensors were realized by immobilizing onto gold nanoparticles (AuNPs) via a thiol spacer the hpDNA constituted by the heptamer loops and the same double helix stem of four base pairs (GAAG at 5′ and CTTC at 3′ end). The HpDNA-AuNP was used to modify the surface of 20 MHz quartz crystal microbalances (QCMs). The realized E-nose was able to clearly discriminate among 15 pure VOCs of different chemical classes, as demonstrated by hierarchical cluster analysis. The analysis of real beer samples during fermentation was also carried out. In such a challenging matrix consisting of 23 different VOCs, the hpDNA E-nose with heptamer loops was able to discriminate among different fermentation times with high success rate. Class assignment using the Bayes theorem gave an excellent 98% correct beer samples classification in cross-validation.