Chemiluminescence (CL) imaging, characterized by its high signal-to-noise ratio, has emerged as a highly promising approach for noninvasive and efficient tumor detection. Nevertheless, the development of efficient near-infrared (NIR) emission CL probes with good biocompatibility for precise tumor diagnosis remains a challenge. In the present study, we designed and synthesized a biocompatible NIR CL nanoparticle with aggregation-induced emission characteristics, named CPPO/BSA@ AuNCs. Specifically, bis(2,4,5-trichloro-6-carbopentoxyphenyl) oxalate (CPPO) was encapsulated by bovine serum albumincapped gold nanoclusters (BSA@AuNCs) with aggregationinduced NIR emission properties. The nanoprobe demonstrated high CL signals with an extremely long lifetime and could be employed for quantitative analysis of reactive oxygen species, such as H 2 O 2 . Importantly, the NIR CL signal could effectively penetrate tissues with a penetration depth exceeding 27 mm, exhibiting significantly superior performance compared to the NIR fluorescence signal and blue CL signal. In vivo studies using mice bearing the 4T1 primary breast tumor and intraperitoneal metastases demonstrated that nanoprobe-based NIR CL imaging could effectively distinguish tumors from normal tissues, paving the way for CL-guided deep tumor diagnosis and surgery.