Cooking oil fumes (COFs) represent a major indoor environmental pollutant and exhibit potent mutagenic or carcinogenic health effects caused by containing various heterocyclic aromatic amines (HAAs) and long-chain aldehydes. Despite some evaluation of the relationship between cumulative exposure to COFs and lung cancer, mainly focused on high concentration exposure to cancer cells, and cell damage of HAAs and aldehydes with low dose exposure to healthy cells has been unadequately investigated. Herein, we have firstly scrutinized the toxicity of these three typical compounds of HAAs and aldehyde emission from COFs, which includes heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 3,8-dimethylammidazo[4,5-f]quinoxalin-2-amine (MeIQx) and trans, trans-2,4-decadienal (TDA)) to both in vitro and in vivo. In vitro experiments revealed that the PhIP, MeIQx and TDA aerosol particles had negligible toxicity to cancer cells (A549 and HepG-2) but strong cytotoxicity to normal healthy cells (HelF and L02) under 0.5-4 µg/mL low dose exposure based on the reactive oxygen species (ROS) mechanism. Furthermore, the in vivo data demonstrate that PhIP causes significant damage to the lung and liver after monitoring mice after 30 days of exposure to a larger amount of PhIP. These results indicate direct proof of COFs damage even at low exposure to HAAs and aldehydes.