Controlling avoidable causes of cancer may save cancer-related healthcare costs and indirect costs of premature deaths and productivity loss. This study aimed to estimate the economic burden of cancer attributable to major lifestyle and environmental risk factors in Japan in 2015. We evaluated the economic cost of cancer attributable to modifiable risk factors from a societal perspective. We obtained the direct medical costs for 2015 from the National Database of Health Insurance Claims and Specific Health Checkups of Japan, and estimated the indirect costs of premature mortality and of morbidity due to cancer using the relevant national surveys in Japan. Finally, we estimated the economic cost of cancer associated with lifestyle and environmental risk factors. The estimated cost of cancer attributable to lifestyle and environmental factors was 1,024,006 million Japanese yen (\) (8,460 million US dollars [$]) for both sexes, and \673,780 million ($5,566 million) in men and \350,226 million ($2,893 million) in women, using the average exchange rate in 2015 ($1 = \121.044). A total of \285,150 million ($2,356 million) was lost due to premature death in Japan in 2015. Indirect morbidity costs that could have been prevented were estimated to be \200,602 million ($1,657 million). Productivity loss was highest for stomach cancer in men (\28,735 million/$237 million) and cervical cancer in women (\24,448 million/$202 million). Preventing and controlling cancers caused by infections including Helicobacter pylori, human papillomavirus and tobacco smoking will not only be life-saving but may also be cost-saving in the long run.