AbstractBackgroundLittle is known about the association between liver indicators (The FIB‐4 index, nonalcoholic fatty liver disease fibrosis score (NFS), and fatty liver index (FLI)) and cancer development in patients without preexisting liver disease.MethodsWe conducted a retrospective cohort study with participants who underwent voluntary health checkups and without fatty liver between 2005 and 2018. Our primary outcome was the development of any type of cancer, and its association with each liver indicator was evaluated.ResultsA total of 69,592 participants (mean age: 43.9 years, 29,984 (43.1%) were men) were included. During a median follow‐up of 5.1 years, 3779 (5.4%) patients developed cancer. Compared to participants with a low NFS, those with a medium NFS had a higher risk of developing any type of cancer (adjusted hazard ratio [HR]: 1.18, 95% confidence interval [CI]: 1.07–1.31), whereas those with a medium FIB‐4 index had a decreased risk of developing any type of cancer compared to those with a low FIB‐4 index (adjusted HR: 0.91, 95% CI: 0.83–0.99). Patients with higher scores tended to have a higher risk of digestive organ cancer, regardless of the indicator. A high FLI was also associated with an increased risk of breast cancer (adjusted HR: 2.42, 95% CI: 1.24–4.71); however, those with a medium FIB‐4 index (adjusted HR: 0.65, 95% CI: 0.52–0.81) and NFS (adjusted HR: 0.50, 95% CI: 0.35–0.72) had decreased risks of developing breast cancer compared to those with a high FIB‐4 index and NFS, respectively.ConclusionAmong patients without fatty liver, a higher liver indicator score was associated with an increased risk of cancer in the digestive organs, regardless of the indicator. Notably, those with a medium FIB‐4 index or NFS had a lower risk of developing breast cancer, whereas those with a medium FLI had an increased risk.