Semiconductor metal-oxide/metal heterostructures with plasmonic resonance property are believed to be a reliable substitute for noble-metal surface enhanced Raman scattering (SERS) detection substrate because of their higher sensitivity and lower cost. Here, we demonstrated an ecofriendly and easily-controlled route to synthesize cuprous-oxide/silver (Cu
2O/Ag) heterostructure for sensitive SERS detection of organic dyes by using TEMPO-oxidized cellulose nanofibrils (CNFs) as sole reducing and stabilizing agents. The results showed that Cu
2O cubes were synthesized under mild aqueous conditions, and covered by spherical-like Ag nanoparticles (AgNPs) through substitution reaction. With methylene blue (MB) as a probe, the Cu
2O/Ag heterostructure within the CNF network showed better Raman scattering sensitivity than pure CNF-Cu
2O hybrids at 633 nm laser excitation. When the surface of the Cu
2O cubes was fully covered by AgNPs, the substrate showed the highest SERS activity and reproducibility. The enhancement index was up to 4.0×10
4 and the substrate was capable of detecting MB dyes down to sub part-per million level. The green synthesized CNF-based Cu
2O/Ag heterostructure substrate with improved SERS activity and low fluorescence has great potential in food safety testing, water monitoring and other portable Raman detection devices.