The invention discloses a naphthalene sulfonamide compound and preparation methods and applications thereof. The naphthalene sulfonamide compound provided by the invention can interfere with Keap1-Nrf2 binding and activate Nrf2 so as to alleviate inflammatory damage and improve inflammatory microenvironment, has potential anti-inflammatory activity, and can be used for preparing anti-inflammatory medicine for the inflammatory damage of many inflammation-related diseases. The diseases include chronic obstructive pulmonary disease (COPD), Alzheimer's disease, Parkinson's disease, atherosclerosis, chronic kidney disease (CKD), diabetes, intestinal inflammation, rheumatoid arthritis and the like.