Purpose <p>Heterozygous variants of the <i>KCNQ4</i> gene are associated with isolated sensorineural hearing loss (DFNA2A). This study aimed to determine the frequency and clinical characteristics of pathogenic, likely pathogenic, and uncertain variants in the <i>KCNQ4</i> gene among patients with sensorineural hearing loss of unknown origin in North Spain.</p> Methods <p>We conducted a prospective observational study of patients with sensorineural hearing loss of unknown etiology at a tertiary hospital over six years. Next-generation sequencing carried out with a panel of genes was used to identify genetic variants related to both syndromic and non-syndromic hearing loss.</p> Results <p>Among 370 patients, seven (1.89%) harbored pathogenic or likely pathogenic variants in the <i>KCNQ4</i> gene: c.777_778delinsCC, c.626&#xa0;T &gt; G, and c.778G &gt; C. None of these variants had been previously described. One patient also had a variant of uncertain significance (c.419&#xa0;T &gt; C). All patients exhibited progressive bilateral sensorineural hearing loss, predominantly at high frequencies, with variable onset and severity. None reported dizziness or vertigo. Five patients used hearing aids, and one received a cochlear implant with good results.</p> Conclusions <p><i>KCNQ4</i> gene variants are rare in Cantabria, present in less than 2% of patients with sensorineural hearing loss of unknown origin. Although most variants identified in our study had not been previously described, the observed phenotype aligned with the typical presentation: bilateral, progressive sensorineural hearing loss with variable onset and severity. Some patients may benefit from cochlear implants.</p>