Liddle syndrome (OMIM #177200) is an autosomal dominant disorder caused by gain-of-function pathogenic variants in the genes encoding epithelial sodium channel subunits, including α (SCNN1A), β (SCNN1B), and γ (SCNN1G). The majority of the reported cases carry SCNN1B variants (∼90%), and SCNN1A/G variants are relatively infrequent. Here, we report a 24-year-old Chinese male patient diagnosed with early-onset hypertension. Laboratory tests revealed hypokalemia with a low level of plasma renin activity. Liddle syndrome was confirmed by high-throughput sequencing, which identified a novel nonsense variant Q591X in the SCNN1G gene, resulting in the PY motif’s deletion. The patient’s father has the same mutation, and his mother and sister are normal. All eleven variants in the SCNN1G gene were summarized. Liddle syndrome usually presents with early onset of hypertension with hypokalemia and low-renin activity, but it can be clinically heterogeneous. It is necessary to utilize next-generation sequencing to clarify the diagnosis to identify Liddle syndrome in young patients with hypertension and to perform early treatment and prevent a series of adverse outcomes caused by hypertension.