Black phosphorus quantum dots (BPQDs) as novel nanomaterials have many potential applications in biomedicine. However, the interaction of BPQDs with proteins and their biological effects and potential risks are still unclear. Here, mucin, which serves biologically as a physical barrier against foreign substances entering tissues, was chosen as a model substrate for studying the adsorption desorption behavior of BPQDs using surface plasmon resonance sensing and a quartz crystal microbalance with dissipation monitoring. We found that the surface modification of BPQDs with poly(ethylene glycol)-amine (PEG-NH2) reduces the adsorption rate of the quantum dots but increases their adsorbed amount on the mucin surface. The pH value, ionic strength, and ionic valence also had significant effects on the adsorption behavior of BPQDs. Upon increasing the pH from 2 to 7, the amount of BPQD adsorption decreased from 14.1 to 3.2 ng/cm(2). A high ionic strength and ionic valence (e.g., Mg2+, Al3+) also inhibit the surface adsorption of BPQDs. Furthermore, the adsorption desorption mechanisms of BPQDs on the mucin surface were proposed. The adsorption-desorption behavior under different conditions may be attributed to the steric hindrance of PEG, the electrostatic interaction, and/or charge screening. These findings provide useful insights into the interfacial behavior of BPQDs before they enter the tissues.