The study introduces a method called LLPS-CLIR-MS (liquid-liquid phase separation cross-linking of isotope-labeled RNA coupled to mass spectrometry) to investigate protein-RNA interactions within biomolecular condensates. This method combines UV cross-linking of protein-RNA interactions with mass spectrometry to characterize intermolecular interactions at residue-specific resolution. The authors apply this method to several protein-RNA complexes, including PTBP1-RNA and FUS-RNA, and demonstrate that sequence-specific interactions between RNA and RBPs are maintained inside condensates. They also identify structural alterations at protein-RNA interfaces, such as additional unspecific contacts in the condensed phase. The study provides insights into the role of specific protein-RNA interactions in the multivalent network within condensates and suggests that these interactions contribute to phase separation. The LLPS-CLIR-MS method is valuable for structural characterization of protein-RNA complexes in the condensed phase, potentially enabling the determination of their structure.The study introduces a method called LLPS-CLIR-MS (liquid-liquid phase separation cross-linking of isotope-labeled RNA coupled to mass spectrometry) to investigate protein-RNA interactions within biomolecular condensates. This method combines UV cross-linking of protein-RNA interactions with mass spectrometry to characterize intermolecular interactions at residue-specific resolution. The authors apply this method to several protein-RNA complexes, including PTBP1-RNA and FUS-RNA, and demonstrate that sequence-specific interactions between RNA and RBPs are maintained inside condensates. They also identify structural alterations at protein-RNA interfaces, such as additional unspecific contacts in the condensed phase. The study provides insights into the role of specific protein-RNA interactions in the multivalent network within condensates and suggests that these interactions contribute to phase separation. The LLPS-CLIR-MS method is valuable for structural characterization of protein-RNA complexes in the condensed phase, potentially enabling the determination of their structure.