Two-dimensional materials-based field-effect transistors (FETs) are promising biosensors because of their outstanding electrical properties, tunable band gap, high specific surface area, label-free detection, and potential miniaturization for portable diagnostic products. However, it is crucial for FET biosensors to have a high electrical performance and stability degradation in liquid environments for their practical application. Here, a high-performance InSe-FET biosensor is developed and demonstrated for the detection of the CA125 biomarker in clinical samples. The InSe-FET is integrated with a homemade microfluidic channel, exhibiting good electrical stability during the liquid channel process because of the passivation effect on the InSe channel. The InSe-FET biosensor is capable of the quantitative detection of the CA125 biomarker in breast cancer in the range of 0.01-1000 U/mL, with a detection time of 20 min. This work provides a universal detection tool for protein biomarker sensing. The detection results of the clinical samples demonstrate its promising application in early screenings of major diseases.