The human respiratory syncytial virus (HRSV) core viral RNA polymerase comprises the large polymerase protein (L) and its co-factor the phosphoprotein (P) which associate with the viral ribonucleoprotein complex to replicate the genome and, together with the M2-1 protein, transcribe viral mRNAs. Whilst cellular proteins have long been proposed to be involved in the synthesis of HRSV RNA by associating with the polymerase complex, their characterization has been hindered by the difficulty of purifying the viral polymerase from mammalian cell culture. In this study, EGFP-tagged L and P protein expression was coupled with high affinity anti-GFP antibody-based immunoprecipitation and quantitative proteomics to identify cellular proteins that interacted with either the L or the P proteins when expressed as part of a biologically active viral RNP. Several core groups of cellular proteins were identified that interacted with each viral protein, including in both cases, protein chaperones. Ablation of chaperone activity using small molecule inhibitors confirmed previous studies, which suggested this class of proteins acted as positive viral factors. Inhibition of HSP90 chaperone function in the current study showed that HSP90 was critical for L protein function and stability, whether in the presence or absence of the P protein. Inhibition studies suggested that HSP70 also disrupted virus biology and might help the polymerase remodel the nucleocapsid to allow RNA synthesis to occur efficiently. This indicated a pro-viral role for protein chaperones in HRSV replication and demonstrates that the function of cellular proteins can be targeted as potential therapeutics to disrupt virus replication.