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Steroidal glycoalkaloids (SGAs) are a class of nitrogen-containing glycosides occurring in several plant families and biosynthesized through a specific pathway. HMG-CoA reductase is the first enzyme of this pathway, and its transcription can be regulated by biotic and abiotic stressors and even in a tissue-specific manner. This study aimed to characterize the <i>HMG</i> genes family in a tuber-bearing potato species, <i>Solanum commersonii</i>, using transcriptional and functional approaches. Our results provided evidence that four <i>ScHMGs</i> with different tissue-specificities represent the <i>HMG</i> gene family in <i>S. commersonii</i> and that they originated from <i>ScHMG1</i> through segmental duplications. Phylogenetic analysis suggests that <i>ScHMG1</i> is the direct ortholog of <i>AtHMG1</i>, which is associated with SGAs accumulation in plants. Its overexpression in <i>S. commersonii</i> revealed that this gene plays a key role in the accumulation of glycoalkaloids regulating the production of dehydrocommersonine.