Here, we showed that upregulated HSPA1L in ALDH1high cells sorted from NSCLC A549 cells was involved in insulin-like growth factor-1 receptor β IGF1Rβ activation and enhanced the CSC-like properties, resistance, and malignancy via either the AKT/NF-κB or AKT/GSK3β/β-catenin signaling pathways. The gene discussed is HSPA1L; the disease is non-small cell lung carcinoma.