A total of 38 hazardous constituents in mainstream cigarette smoke of low-yield cigarettes sold in Korea were selected and analyzed using established methods. Risk calculations were performed using risk algorithms employed in previous studies and Korean population-based exposure parameters. The median cumulative incremental lifetime cancer risk of male smokers could vary from 828 × 10−6 to 2510 × 10−6, and that of female smokers could range from 440 × 10−6 to 1300 × 10−6, depending on the smoking regimens. The median hazard index as the sum of hazard quotients of male smokers varied from 367 to 1,225, and that of female smokers varied from 289 to 970, depending on the smoking regimens. The sensitivity analysis for this risk assessment indicated that the constituent yields in mainstream cigarette smoke, average number of cigarettes smoked per day or year, and mouth-spill rate are the main risk factors. Statistical positive correlations between the average daily dose calculated by the exposure algorithm used in this study for individual smokers and biomarkers verified the reliability of this assessment. It could be concluded that inhalation of the constituents present in the mainstream of low-yield cigarettes has significant cancer and non-cancer health risks, although its effect on risk reduction is still unknown under the fixed machine-smoking conditions.