Posttranslational modifications (PTMs) of core histones, such as histone methylation, play critical roles in a variety of biological processes including transcription regulation, chromatin condensation and DNA repair. In T. brucei, no domain recognizing methylated histone has been identified so far. TbTFIIS2-2, as a potential transcription elongation factors in T. brucei, contains a PWWP domain in the N-terminus which shares low sequence similarity compared with other PWWP domains and is absent from other TFIIS factors. In the present study, the solution structure of TbTFIIS2-2 PWWP domain was determined by NMR spectroscopy. TbTFIIS2-2 PWWP domain adopts a global fold containing a five-strand β-barrel and two C-terminal α-helices similar to other PWWP domains. Moreover, through systematic screening, we revealed that TbTFIIS2-2 PWWP domain is able to bind H4K17me3 and H3K32me3. Meanwhile, we identified the critical residues responsible for the binding ability of TbTFIIS2-2 PWWP domain. The conserved cage formed by the aromatic amino acids in TbTFIIS2-2 PWWP domain is essential for its binding to methylated histones.