This study investigaved the digestion performance and microbial community structure in the solid-state co-digestion (ScoD) of food waste (FW) and highland barley straw (HBS, mixing ratio of 1:1, 1:5, and 5:1, labeled as FH11, FH15, and FH51, respectively) using different inoculum-substrate ratios (ISR, 2:1, 3:1, and 5:1, labeled as ISR21, ISR31, and ISR51, respectively). The results showed that the cumulative methane yield (CMY) increased with increasing ISR (274.9-410.1, 246.3-411.5, 268.2-451.9 mL/gVS in ISR21, ISR31, and ISR51, respectively). The ScoD of FH51 achieved the maximum CMY with all ISR ratios. The hydrolysis rate coefficient increased under high ISR conditions. The microbial community structure varied in response to different ISR, with Fastidiosipila, Aminobacterium, Gallicola, Methanobacterium, Methanoculleus, and Methanosphaera being the dominant genera. Bacterial genera were strongly correlated with digestion performance and operational parameters. Consequently, controlling the ISR is an effective strategy for imporoving the performance of ScoD.