Strong evidence for decreased risk of hepatocellular carcinoma (HCC) in relation to statin initiation in non-alcoholic fatty liver disease (NAFLD) patients was generated in this study.

Observations indicate that statin can be employed as a protective medication for NAFLD patients to attenuate the risk of HCC.

• Recent evidence indicates potential clinical advantages of statin in cancer chemoprevention and treatment.

• The Optum de-identified Clinformatics database was used in this study including 272,431 adults with NAFLD diagnosis.

• In the inverse probability of treatment weighting model, a 53% less risk of developing HCC was present in statin initiators vs nonusers (hazard ratio,HR: 0.47).

• In the sub-cohort with FIB-4 data available, statin initiation was found to be related to a 56% hazard reduction of developing HCC in NAFLD post-adjusting for FIB-4 score (HR: 0.44).

• For both lipophilic statin and hydrophilic statin, the relationship between statin initiation and lower risk of HCC development was evident, with HRs 0.49 and 0.40, respectively.

• A greater hazards reduction was obvious as the dose and duration of statin use increased.

• A 70% decrease in hazards of developing HCC (HR: 0.30) was noted in relation to more than 600 cumulative defined daily doses of statin use, among NAFLD patients.