mutation is a biomarker for guiding multiple solid tumor treatment. However, the prevalence of large genomic rearrangements (LGRs) in Chinese cancer patients has not been well revealed partially due to technical difficulties in LGR detection. This study utilized next-generation sequencing (NGS) to analyze the mutation profile, including LGR, in 56126 Chinese cancer patients. We also reported that two ovarian and breast cancer patients with NGS-determined LGR benefited from PARP inhibitors (PARPi). DNA sequencing identified variants (including LGR, pathogenic and likely-pathogenic variants) in 2108 individuals. Seventy patients were discovered to harbor germline LGRs in and 14 had germline LGRs in . Among the LGRs detected, exon 1-2 deletion was the predominant LGR (14/70) in , and exon 22-24 deletion was the most frequent LGR (3/14) in . Notably, the exon 7 deletion was a novel LGR and was identified in six patients, suggesting a specific LGR in Chinese cancer patients. The prevalence analysis of and LGRs across multiple cancers revealed that LGR more frequently occurred in ovarian cancer (1.31%, 33/2526), and LGR was more commonly seen in cholangiocarcinoma (0.47%, 2/425). Two ovarian and breast cancer patients with LGR benefited from PARPi therapy. This is the first study to reveal the LGR profile of a Chinese pan-cancer cohort by using an NGS-based assay. Two breast and ovarian cancer patients harboring NGS-determined LGR benefited from PARPi, indicating that NGS-based detection of LGR has the potential to guide PARPi treatment.