Overall, for the first time, our data demonstrated that circHERC1 plays an oncogenic role in lung cancer development via miR-142-3p/HMGB1 axis which enhanced the expression of HMGB1 to activate the MAPK/ERK and NF-κB pathways by sponging miR-142-3p in cancer cells. This evidence concerns the gene HMGB1 and cancer.