Background: Li-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome, mainly caused by the lack of tumor suppressor gene TP53. The LFS related tumors include breast cancer, brain tumors, malignant sarcoma, bone cancer and central nervous system tumors. In addition to TP53 germline mutations, studies have shown that CHEK2 is also a susceptibility gene for LFS, and CHEK2 germline mutations is related to a series of cancer types. However, the correlation between tumor mutation burden (TMB), age, gender, PD-L1 expression and TP53 or CHEK2 germline mutations in malignant tumors remains unknown. Methods: In this study, we retrospectively analyzed the mutation characteristics of TP53 or CHEK2 germline mutations in patients with solid tumors without selecting age or family history. We identified 631 patients harboring TP53 or CHEK2 mutations from 9337 patients with malignant solid tumors. According to the ACMG (American College of Medical Genetics and Genomics) guidelines in pathogenicity, the 631 patients in the retrospective cohort were divided into three groups, including P/LP group (with pathogenic or likely-pathogenic mutations), VUS group (with uncertain significance mutations) and B/LB group (with benign or likely-benign mutations). We also analyzed the differences in TMB, age, gender and PD-L1 expression among the three groups. Statistical significance was defined as P-value less than 0.05. Results: The 631 (631/9337) patients carried TP53 or CHEK2 germline mutations were identified, in which 33 patients with pathogenic mutations and 15 patients with likely-pathogenic mutations. These pathogenic or likely-pathogenic mutations mainly occurred in lung cancer, brain tumors, colorectal cancer and liver cancer, accounting for about 35.4%, 20.8%, 16.7% and 12.5%, respectively. Among the three groups, TMB was significantly different between P/LP group and B/LB group (P = 0.037), and the B/LB group was higher. In addition, we found that the three groups had no significant differences in age, gender and PD-L1 expression. Conclusions: Our data showed that 0.823% (48/8535) malignant solid tumor patients carried TP53 (28/48) or CHEK2 (20/48) germline pathogenic or likely_ pathogenic mutations. In addition, the TMB value in B/LB group was significantly higher than that in P/LP group. The other characteristics of LFS will be studied in the future.