To validate the clinical significance of telomere length, we analyzed the variation and the prognostic value of telomere length in an independent cohort of 371 HCC patients from TCGA 13. This cohort included 318 HCC patients with paired tumor and blood samples, as well as 53 HCC paired tumor and normal liver tissues (Figure 5A). Telomere length was quantified based on the linear mixed modeling adjusted high‐confidence whole‐genome sequencing (n = 54) and whole‐exome sequencing (n = 317) data. Consistent with our results, 81.94% of 371 samples displayed telomere attrition in tumor tissues (median 0.19; IQR 0.13–0.84) compared with normal controls (median 0.28; IQR 0.23–0.68) (p < 0.001; Figure 5B). Of note, 262 of 318 paired tumor and blood samples (82.38%) showed significant telomere attrition in tumor tissues (median 0.17; IQR 0.13–0.33) compared with the blood samples (median 0.27; IQR 0.22–0.35) (p < 0.001; Figure 5C). Likewise, 79.25% of 53 HCC patients with paired tumor and normal liver tissues had shorter telomeres in tumor (median 1.25; IQR 0.23–3.38) than in paired normal tissues (median 1.63; IQR 0.32–5.21), although no statistically significant difference was detected (p = 0.144; Figure 5D), probably due to the small sample size.