Updated project metadata. Cigarette smoke (CS) causes adverse health effects that may occur shortly after smoking initiation and lead to the development of respiratory disease (chronic obstructive pulmonary disease), cardiovascular disease, and cancer. To reduce the risk of smokers developing smoking-related diseases, Philip Morris International is developing modified risk tobacco products (MRTP). Within a systems toxicology study, we integrated multi-omics measurements with classical endpoints to assess the effects in female ApoE-/- mice of six months of exposure to CS (at 29.9 µg nicotine/L) or to aerosols from one potential and one candidate MRTP (CHTP 1.2 and THS 2.2, respectively) at matched nicotine concentrations. The impact of cessation or switching to CHTP 1.2 after three months of CS exposure was also evaluated. This data set contains the results from the analysis of proteome changes in the liver using the iTRAQ® quantification approach.