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Introduction: Assessment of actionable gene mutations and oncogene fusions have made a paradigm shift in treatment strategies of non-small cell lung cancer (NSCLC). <i>HRAS</i> mutations involved around 0.2–0.8% of NSCLC patients, mostly on codon 61. For these patients, few data are available regarding clinical characteristics and response to therapies. Methods: Next-Generation Sequencing (NGS) done routinely at Nantes University Hospital was used to identify <i>HRAS</i> molecular alterations in NSCLC patients. We identified and described four <i>HRAS</i> p.GlnQ61Leu mutated patients. Literature of previously <i>HRAS</i>-mutant NSCLC cases was reviewed, and available data in solid tumour with the most advanced H-Ras specific inhibitor, tipifarnib, were presented. Results: Of 1614 patients diagnosed with advanced NSCLC from January 2018 to December 2020, four (0.25%) had <i>HRAS</i> p.Gln61Leu mutation. Three of them died during the first-line systemic therapy. Furthermore, three additional cases were identified in literature. All cases were current or former smokers, most of them had pleural or pericardial effusion at diagnosis. Conclusions: The clinical course of patients with <i>HRAS</i>-mutant NSCLC remains unclear. Furthers cases should be identified in order to clarify prognosis and response to therapies. Tipifarnib, a farnesyl transferase inhibitor, is a promising candidate to target <i>HRAS</i>-mutant tumours and should be explored in NSCLC patients.