- C-reactive protein (CRP) is a plasma protein that is one of the most expressed proteins in acute phase inflammation cases. It is a well-known biomarker for inflammatory disorders. There is a significant correlation between increasing CRP concentration and the risk of being exposed to cardiovascular diseases (CVD) and sepsis; thus, monitoring and quantifying CRP levels in a simple, inexpensive, and quick manner can improve clinical diagnostics and help prevent major inflammatory conditions. Here a nanobiosensor was developed, benefiting from the LSPR property of gold-nanorod (GNR) to measure CRP concentration. Nanorods were fabricated using One-pot synthesis by trimethyl ammonium bromide (CTAB) as a surfactant. This method provides the advantage of both step and time reduction in synthesis and decreases the contamination probability of nanorods as the products. The nanorods were characterized using TEM with an average size of (24 ± 1 nm) × (5 ± 1 nm) and a typical aspect ratio of ∼4.9. The surface of the rods was modified with a specific aptamer for the target protein, and the LSPR shifts due to the gold nanorod's refractive index change as the result of protein interaction with the biosensor investigated using a 100-900 nm UV absorption device. The results indicated that the nanobiosensor could respond to different CRP concentrations within 30 min. The selectivity test has shown nonresponsive results of nanobiosensor to BSA and TNF-α proteins which are used to evaluate the biosensor behavior in non-target proteins. The detection limit was evaluated at 2 nM, and the sensor's linear response ranged between 2 - 20 nM.