Background: The Ataxia-telangiectasia mutated (ATM) gene is an oncosuppressor, which plays an important role in the repair of DNA double-strand breaks (DSBs). The mutation profiles of ATM gene in Chinese solid tumor patients can help understand pathogenesis, prognosis, and identify targets for therapy. Methods: Using commercial NGS assays, we retrospectively analyzed genomic DNA alterations in normal-paired samples from 1351 patients with malignancies from January 2021 to October 2022, and alterations including single base substitution, short and long insertion/deletions, copy number variations, gene fusions and rearrangements. Results:ATM gene was altered in 6.8% (92 of 1351) of all solid tumors. The frequency of ATM variations was assessed in multiple cancer types, including non-small cell lung cancer 22% (35/159), endometrial carcinoma 15% (2/13), biliary tract tumor 12.1% (7/58), gastric cancer 10.7% (3/28), prostatic cancer 8.3% (1/12), breast cancer 6.7% (2/30), colorectal cancer 6.5% (11/168), thyroid cancer 6.2% (5/80), cervical carcinoma 5.7% (2/35), prostatic cancer 3.9% (2/51), liver cancer 3% (2/66). A total 102 genetic alterations were identified in 92 patients, including 70 missense mutations (69%), 14 nonsense (14%), 9 splicing (9%), 3 frameshift (3%), 2 deletion (2%), 2 copy number variation (2%). Among these patients, 2 had pathogenic germline ATM heterozygous mutations, including one lung adenocarcinoma and one pancreatic cancer. Furthermore, in our cohort, ATM mutation carriers also owned other actionable mutation, the most frequent one was TP53 (41%), followed by APC (29%), KRAS (23%), MLL3 (22%) and BRCA2 (20%). Conclusions: Our findings indicate that ATM alterations are widely mutated in Chinese multiple cancer types, with specific mutations differing largely among different tumor types. ATM alterations warrant further investigation as predictive biomarkers of response to PARP inhibitors or platinum-based therapy.