Vascular endothelial growth factor (VEGF) is directly related to cancer growth and its distant spread, and thus, it is considered a promising biomarker for diagnosis and post-treatment monitoring of patients with malignancies. Zinc protoporphyrin (ZnPP) is a zinc-centered raw purple compound (protoporphyrin) that has unique optical and electrochemical characteristics. In this study, we used a ZnPP-modified gold electrode to generate a chemical bond with Avastin by self-assembly and fabricate a Au/ZnPP/Avastin electrode. Bovine serum protein (BSA) was added to the electrode to prevent non-specific linkage with biomolecules. The prepared Au/ZnPP/Avastin/BSA electrodes were used for the detection of VEGF by cyclic voltammetry and amperometry. The optical properties of ZnPP were analyzed with an ultraviolet/visible/near-infrared spectrometer and a photoluminescence spectrometer. The structural and hydrophilic/hydrophobic properties of the ZnPP-modified gold electrodes were investigated by Fourier-transform infrared spectroscopy and contact angle gauge, respectively. VEGF was detected with the Au/ZnPP/Avastin/BSA electrodes prepared either with (w/LT) or without light treatment (w/o LT). The w/LT electrode showed a linear range and a sensitivity of 0.1 pg/mL–10 ng/mL and 6.52 μA/log(pg/mL)-cm2, respectively; the corresponding values for the w/o LT electrode were 10 pg/mL–10 ng/mL and 3.15 μA/log(pg/mL)-cm2, respectively. The w/LT electrode had good specificity for VEGF and was minimally influenced by other molecules. The excellent detection range, high sensitivity, and high selectivity for VEGF detection indicate that Au/ZnPP/Avastin electrodes have great potential for diagnostic and prognostic applications in patients with malignancies.