Although the non-small cell lung cancer (NSCLC) is one of the most malignant tumours worldwide， the mechanisms controlling NSCLC tumourigenesis remain unclear. Here， we find that the expression of miR-520b is up-regulated in NSCLC samples. Further studies have revealed that miR-520b promotes the proliferation and metastasis of NSCLC cells. In addition， miR-520b activates Hedgehog (Hh) pathway. Inhibitor of Hh pathway could relieve the oncogenic effect of miR-520b upon NSCLC cells. Mechanistically， we demonstrate that miR-520b directly targets SPOP 3'-UTR and decreases SPOP expression， culminating in GLI2/3 stabilization and Hh pathway hyperactivation. Collectively， our findings unveil that miR-520b promotes NSCLC tumourigenesis through SPOP-GLI2/3 axis and provide miR-520b as a potential diagnostic biomarker and therapeutic target for NSCLC.