BackgroundHighly sensitive and accurate monitoring of disease biomarkers is of substantial importance for early clinical diagnostic aims. Prostate cancer is one of the most prevalent malignancies of the male genitourinary system. It is of great significance to fabricate accurate and reliable diagnostic assay for prostate cancer disease. Prostate-specific antigen (PSA) is a prostate cancer biomarker secreted from the prostate epithelial cells. In this study, a tag-free aptasensor is introduced for the ultrasensitive determination of PSA ultralow levels by incorporating liquid crystal (LC) molecules at the surfactant-regularized interface. MethodRelying on the orientational changes of LCs at the surfactant-arranged interface, PSA can be detected by the LC aptasensor. The optical vision of the aptasensor background changes from colorful to dark by forming the aptamer-PSA complex that induces the re-arrangement of LC molecules from disordered to homeotropic direction. ResultsThe aptasensor can monitor PSA in the concentration range of 1–1200 pg mL−1 with a detection limit of 0.148 pg mL−1. Besides, PSA levels can be monitored in the real human serum samples by using the LC aptasensor. ConclusionThe developed aptasensor benefits the superiorities of low cost, simplicity, easy-to-carry, operator-free, and great sensitivity, making it novel as a portable diagnostic tool. With the capability to quantify PSA in real human serum samples, the LC aptasensor is efficient in the field of health care monitoring.