Although the HA/CD44 axis and their role in lung tumorigenesis have been previously described, we reported for the first time a correlation between HA and CSC phenotype, together with a role in cancer progression and clinical outcomes since patients with a higher expression of HAS3, HAS2, ABCC5, SOX2, and ALDH1 showed a decrease in their disease-free intervals. Here, SOX2 is linked to cancer.