Differential gene expression based on RNA-seq is widely used.Bioinformatics skills are required since no algorithm is appropriate for all experimental designs.Moreover, when working with organisms without reference genome, functional analysis is less than straightforward in most situations. DEgenes Hunter, an attempt to automate the process, is based on two independent scripts, one for differential expression and one for functional interpretation. Based on replicates, the R script decides which of the edgeR, DEseq2, NOISeq and limma algorithms are appropriate. It performs quality control calculations and provides the prevalent, most reliable, set of differentially expressed genes, and lists all other possible candidates for further functional interpretation. It also provides a combined P-value that allows differentially expressed genes ranking. It has been tested with synthetic and real-world datasets, showing in both cases ease of use and reliable results. With real data, DEgenes Hunter offers straightforward functional interpretation.