Background: Lynch syndrome (LS) caused by germline pathogenic variants (PVs) in mismatch repair (MMR) genes, which increased risk of malignancy in different organs. LS-related tumors included colorectal, endometrial, gastric, ovarian, pancreas, urinary system, biliary tract, central nervous system, skin and small intestinal carcinomas (CRC, EC, GC, OC, PC, UST, BTC, CNST, SC, SIC). As sequencing technology becomes more economical and widespread, more MMR PVs were detected in LS-unrelated tumors. The aim of this study was to explore the clinical characterization in Chinese real-world LS solid tumor. Methods: We applied next-generation sequencing (NGS) screening to detect the germline mutation in MMR (include MLH1, MSH2, MSH6, PMS2), tumor mutation burden (TMB) and microsatellite instability (MSI) in Chinese solid tumor patients (pts). In the cohort, lung cancer (LC) was the most common cancer type, followed by CNST, CRC, hepatic carcinoma (HC). Results: 149 LS pts were observed in our cohort, among which 81.2% (121/149) carried LS-related tumors (44 CRC, 47 CNST, 9 EC, 9 BTC, 4 UST, 3 OC, 2 GC, 2 SC, 1 SIC), 18.8% (28/149) carried with LS-unrelated tumors(18 LC, 5 HC, 3 sarcoma, 1 ampullary carcinoma, 1 peritoneal cancer), and the age showed no significant difference between LS-related tumors and LS-unrelated tumors (average age: 48 vs 53, p=0.08). The distribution of MMR PVs were as follows: MLH1 (37, 24.8%), MSH2 (46, 30.9%), MSH6 (34, 22.8%), PMS2 (32, 21.5% ), and comparative analysis showed that LS-related tumors tended to carry MLH1 and MSH2 PVs (60.3%, 73/121), while LS-unrelated tumors tended to carry MSH6 and PMS2 PVs (67.9%, 19/28) (p<0.05). 46.3% LS pts had MSI-H, concentrated in MLH1 or MSH2 PVs carriers. MSI-H showed a higher detection rate in LS-related tumors other than LS-unrelated tumors(56.1% vs 3.6%, p<0.005). Among LS-related tumors, the top 3 prevalence of MSI-H were CRC (93.2%, 41/44), BTC (55.6%, 5/9) and EC (44.4%, 4/9), which were lower in CNST (31.9%, 15/47). In addition, we found that the rate of TMB-H in LS-related tumors was also higher than LS-unrelated tumors (p<0.001). Conclusions: In our dates, 18.8%(28/149) LS pts carried with LS-unrelated tumors, which emphasized the importance of germline genetic assessment for LS in pan-cancer. In addition, MSI-H, TMB-H and MMR PVs distributions were significantly different in LS-related tumors and LS-unrelated tumors. The differences about LS clinical characterization associated with MMR genes require further study.