Cardiovascular diseases have become the number one killer of human health. Early diagnosis and treatment of cardiovascular diseases can effectively improve the treatment effect and reduce the disease death rate. As an important marker of cardiovascular disease, Low-Density Lipoprotein (LDL) can be used for the early detection of cardiovascular disease. In this study, a novel carbon-based Light Addressable Potentiometric Sensor (C-LAPS) for determination LDL has been constructed based on o-phenylenediamine modified nitrogen-doped graphene quantum dots/reduce graphene oxide (OPD@NGQDs/rGO) photosensitive layer. The OPD@NGQDs/rGO photosensitive layer has excellent photoelectric conversion efficiency, large specific surface area and good biocompatibility to enhance the response signal. For the determination LDL by the C-LAPS system, LDL binding to LDL aptamer causes a change in the surface potential of the photosensitive layer, producing a response signal that can be detected by the I-V curve. Under optimal conditions, the C-LAPS had a good linear relationship with LDL concentration in the range of 0.01 μg/mL- 0.15 μg/mL. The sensitivity was 1819 mV/µg·mL−1 and the limit of detection (LOD) was 6.43 ng/mL (S/N = 3). In addition, the C-LAPS showed good specificity, reproducibility, stability and satisfactory relative error for detecting LDL in human serum samples. Therefore, the C-LAPS has good performance and demonstrates potential clinical value.