Abstract Backgrounds: Cancer is the most common cause of mortality in Korea. According to International Agency for Research on Cancer (IARC), tobacco smoking is the Group I carcinogen, and the National Cancer Center Korea reported in 2009 that 20.9% and 2.3% of total cancer incidence were attributable to tobacco smoking in men and women, respectively. As of 2020, we estimated population attributable fraction (PAF) of cancer incidence due to tobacco smoking. Methods: We organized the Consensus Committee to develop strategy and methodology for PAF estimation. From the consensus, cancer sites for PAF estimation were selected based on the IARC list of classification with sufficient evidence in human. PAF was calculated by using Levin’s formula which includes exposure prevalence and relative risk (RR). Exposure prevalence was collected from the Korea National Health and Nutrition Examination Survey (KNHANES) in 2005, assuming that latent period from risk exposure to cancer development was 15 years. Tobacco smoking was defined as a categorical variable including non-smokers, past smokers, and current smokers. Pooled RRs were estimated from meta-analysis of RRs obtained from Korean Genome and Epidemiology Study, National Health Examination data provided by National Health Insurance Services, Korean Cancer Prevention Study-II, and KNHANES, each of which was linked with Korea Cancer Registry. Cox proportional hazards model were used to estimate RRs, while adjusted by age groups and alcohol consumption. Results: For men, 17.4% of all cancer cases were attributed to smoking, compared to 1.7% for women. Specifically, in men, 57.9% of lung cancer, 36.4% of bladder cancer, 31.9% of esophageal cancer, 39.1% of laryngeal cancer, 25.4% of oral cavity/pharyngeal cancer, 19.7% of liver cancer, and 19.5% of stomach cancer were attributed to tobacco smoking. In women, 51.7% of laryngeal cancer, 15.0% of esophageal cancer, 11.6% of lung cancer, 6.0% of bladder cancer, 5.1% of oral cavity/pharyngeal cancer, 5.0% of cervix cancer, and 4.6% of liver cancer were due to smoking. Conclusion: Tobacco smoking is an important cause of esophageal, laryngeal, and lung cancer in men, and esophageal and laryngeal cancer in women, and comprises a substantial proportion of PAF in cancer incidence. Thus, intervention measures are needed to reduce smoking prevalence for cancer prevention in Korea. Citation Format: Su Jung Byoun, Yoon-Jung Choi, Ye Lin Min, Sue-Kyung Park, Kwang Pil Ko, So_Seul Sung, NaYoung Kim, Keum Ji Jung, Sun Ha Jee, Sung-II Cho, Min Kyung Lim, Sohee Park, Eun Young Park, Hae Dong Woo, Kyu-Won Jung, E Hwa Yun, Byungmi Kim, Jin-Kyoung Oh, Yoonjoo Choi, Bohyun Park, Hong Gwan Seo, Jeong-Soo Im. Population attributable fraction of tobacco smoking on cancer incidence in 2020 in the Republic of Korea [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2216.