Interferon gamma (IFN-γ), can serve as an active diagnostic biomarker of a broad spectrum of diseases such as auto inflammatory disease, viral and bacterial, parasites infections, and tumor control. The low physiological concentration of IFN-γ at pg‧mL-1 level for most diseases such as tuberculosis and lung cancer demand highly sensitive and selective detection methods. To achieve the goal, a novel paper-based SERS aptasensor towards rapid, dual-modal (visual and ultrasensitive) detection of IFN-γ is presented for the first time. A lateral flow platform with low-cost and user-friendly format in this study is adopted. The detection relies on the competition of the specific aptamer sequence of IFN-γ between its complementary DNA in the test line and IFN-γ in the sample solution. The presence of IFN-γ can be easily observed in the test line by naked eye and detected at pg‧mL-1 level by a portable Raman spectrometer. Linear detection range of 10-2000 pg‧mL-1 could be obtained with detection limit of 8.7 pg‧mL-1. In addition, as low as 10 pg/mL of IFN-γ in human serum could be detected, which is comparable with the results from ELISA.Clinical Relevance- This study establishes a simple, rapid, and low-cost assay for dual-modal detection of IFN-γ, which is in urgent demand in clinics especially vitally important in resource-limited areas.