Telomere shortening has been reported in various human cancers using FISH 28, 29, 30, 31. Shortened telomeres were also found in peripheral blood leukocytes (PBLs) in some human cancers using qPCR 32, 33. Similarly, several studies have demonstrated that telomeres are shorter in HCC compared with peritumor tissues measured by Southern blot or qPCR 34, 35, 36. Investigators had also revealed that telomere shortening occurs in chronic liver diseases 35. However, contrasting conclusions also exist. Higher RTL was found to be associated with aggressive tumor behavior and higher grade in HCC mainly using qPCR 37, 38. RTL of PBLs in HCC was found to be the longest, followed by chronic hepatitis B (CHB) and healthy controls as the shortest, as measured by qPCR 37. The discrepancy in these results may result from the differences in detection methods, specimen sources, and therapeutic schedules. In this study, both qPCR and FISH assays confirmed that telomere shortening occurred in tumor cells and CAFs in over 60% of HCCs compared with their normal counterparts, independently validated in the TCGA dataset. More recently, WES and WGS data showed shorter telomeres in tumors than in normal tissues among 29 of 31 cancer types 13. Thus, telomere shortening should be considered as a common phenomenon in human cancers including HCC. In this respect, there is accumulating data that telomere shortening correlates with cancer susceptibility, such as breast cancer, head and neck squamous cell cancer, and gastrointestinal tumors 39, 40, 41.