Abstract: In order to evaluate the potential hazards of inhaled aerosol from heated tobacco products, a non-targeted chemical analysis method using GC-Orbitrap MS for specific harmful components in aerosol was established. The method consisted of four steps: preliminary identification of comprehensive scoring and retention index (RI), determination of molecular formula under chemical ionization mode, isomer identification via mass spectral fragment ion comparison and chemical standard validation. Both polar and non-polar chromatographic columns were used to analyze the aerosol components from five heated tobacco product samples sourced from China and abroad, and mainstream smoke of 3R4F reference cigarette was also included for comparison. By searching available toxicity databases and combining with reports in literatures, the specific harmful components in the aerosol were identified and screened. The results showed that: 1) A total of 122 specific chemical components were found in heated tobacco product aerosol using the technique, covering various chemical classes, such as aldehydes, ketones, alcohols, esters and amides. Among them, 23 components could be identified by both polar and non-polar chromatographic columns, 47 components could be identified only by polar chromatographic column, and 52 components only by non-polar chromatographic column, respectively. 2) A total of 34 specific harmful components were listed and screened. Among them, 14 components could be identified by both polar and non-polar chromatographic columns, 11 components only by polar chromatographic column, and 9 components only by non-polar chromatographic column. 3) A total of 11 specific harmful components were selected from the 5 heated tobacco product samples, of which 2,5-diformylfuran and 1,2-propanediol 1-acetate had not been reported in heated tobacco product aerosol as harmful component before. This method provides a useful means for screening potential high-risk chemical components emitted by heated tobacco products and could support hazard identification and risk assessment for novel heated tobacco products.