Human-wildlife conflict (HWC) has become a conservation focus for both protected area management and local communities in many parts of the world. The incidence and mediation of HWCs is rooted in coupled environmental and socio-economic contexts. A systematic analysis of HWCs was undertaken in 2016 in the Wolong Nature Reserve located in Sichuan Province, southwestern China. Semi-structured interviews were conducted with 201 local households to understand the occurrence of wildlife damage, the wildlife species involved, the typical losses incurred, and the mitigation measures employed. Results revealed that local HWC has increased rapidly in recent years due to effective biodiversity conservation and ecological restoration policies. Despite the widespread occurrence of HWCs, nearly all respondents stating that they had suffered a financial loss, appropriate compensation schemes are lacking. Local respondents’ expected compensation amount and style were investigated and it was concluded that integrated compensation and community development plans are needed to mediate and resolve HWC. In particular, greater attention should be given to reducing local households’ dependence on agriculture and transforming local livelihood strategies to alternative economic activities not related to farming.