This communication describes a simple sensitive one-step potentiometric aptasensing method for quantitative detection of a referenced therapeutic biomarker (programmed death-ligand 1, PD−L1). The aptasensor is constructed by modifying PD−L1-specific aptamer on TiC-MXene nanosheets-functionalized electrode. Introduction of PD−L1 induces the specific reaction between PD−L1 and aptamer, thereby resulting in the change of spatial structures. The surface electric potential of modified electrode is shifted upon addition of PD−L1 proteins before and after the reaction of aptamer with the analyte. Interestingly, potentiometric aptamer with TiC-MXene nanosheets can achieve a higher sensitivity and a lower detection limit toward target PD−L1 relative to aptamer-modified electrode. Experimental results indicated that the linear range and detection limit of using TiC-MXene nanosheets were 0.01–100 ng mL and 7.8 pg mL PD−L1, respectively. Meanwhile, the specificity, reproducibility, storing stability and accuracy of potentiometric aptasensor are acceptable for the screening of PD−L1 in human serum samples.