Dengue virus (DENV) is a rapidly-spreading mosquito-borne (+)RNA virus that is currently endemic in over 100 countries and responsible for an estimated 390 million yearly infections. Despite an urgent need, safe and effective DENV vaccines or antiviral therapies are not yet available. The DENV non-structural protein 1 (NS1) plays critical roles in viral RNA replication, infectious virus particle production and viral pathogenesis and has emerged as a major target in the development of vaccines and antivirals. Towards the development of antivirals targeting NS1-host factor interactions, we have adopted an APEX2 proximity labelling-coupled quantitative proteomics approach to map the proteomic composition of the DENV NS1 microenvironment in infected cells. The engineered ascorbate peroxidase tag, APEX2, catalyses the conversion of biotin phenol into biotin-phenoxyl radicals that covalently tag proximal endogenous proteins. We have generated and validated an APEX2-tagged dengue reporter virus (DENV2-NS1-APEX2) to enable the biotinylation of NS1-proximal endogenous proteins, optimised the biotinylation reactions and the purification of biotinylated proteins, and acquired preliminary mass spectrometry data identifying these proteins. It is hoped that the characterization of novel DENV NS1-host protein interactions that are essential to the viral replication cycle will identify targets for future antiviral drug development and yield insights into the mechanisms underlying the essential functions of this highly enigmatic protein.