Paper-based lateral flow strips (PLFS) have received increasing attention as point-of-care (POC) tools due to their low cost and simplicity to use. However, PLFS usually suffer from poor sensitivity and serious interference from their sample matrix when they are used with blood plasma containing samples. In our current study, surface-enhanced Raman scattering (SERS) was integrated as the signal transducer into PLFS for protein biomarker detection in blood plasma. Compared with the traditional colorimetric PLFS, the SERS PLFS exhibits advantages in terms of sensitivity and limit of detection (LOD) in a blood plasma sample matrix. These advantages are attributed to the wavelengths of both the excitation light and the Raman scattering signals being able to be tuned into the near-infrared biological window. Herein, our developed SERS PLFS has been successfully demonstrated for detection of neuron-specific enolase (NSE) in diluted blood plasma samples with a LOD of 1 ng/ml. Moreover, these SERS based test strips are in expensive, fast (30 min) and simple to be operated, holding a great potential in assisting screening of traumatic brain injury (TBI) patients in a point-of-care setting.