Quantitative structure-activity-relationship (QSAR) models have application in bioorganic chemistry mainly to the study of small sized molecules while applications to biopolymers remain not very developed. MicroRNAs (miRNAs), which are non-coding small RNAs, regulate a variety of biological processes and constitute good candidates to scale up the application of QSAR to biopolymers. The propensity of a small RNA sequence to act as miRNA depends on its secondary structure, which one can explain in terms of folding thermodynamic parameters. Then, thermodynamic QSAR can be used, for instance, for fast identification of miRNAs at early stages of development such as embryos and stem cells (called here esmiRNAs), and gain clarity inside cellular differentiation processes and diseases such as cancer. First, we calculated folding free energies (DeltaG), enthalpies (DeltaH), and entropies (DeltaS) as well as melting temperatures (T(m)) for 2623 small RNA sequences (including 623 esmiRNAs and 2000 negative control sequences). Next, we seek a QSAR classification model: esmiRNA=0.035 x T(m)-0.078 x DeltaS-8.748. The model correctly recognized 543 (87.2%) of esmiRNAs and 935 (93.5%) of non-esmiRNAs divided into both training and validation series. The model also recognized 908 out of 1000 additional negative control sequences. ROC curve analysis (area=0.93) demonstrated that the present model significantly differentiates from a random classifier. In addition, we map the influence of thermodynamic parameters over esmiRNA activity. Last, a double ordinate Cartesian plot of cross-validated residuals (first ordinate), standard residuals (second ordinate), and leverages (abscissa) defined the domain of applicability of the model as a squared area within +/-2 band for residuals and a leverage threshold of h=0.0074. The present is the first QSAR model for quickly accurate selection of new esmiRNAs with potential use in bioorganic and medicinal chemistry.