The DNA-dependent metalloprotease Spartan (SPRTN) functions in maintaining genomic integrity by participating in the repair of DNA-protein crosslinks (DPCs), a common type of DNA damage. The cytotoxicity of DPCs is attributed to the disruption of cellular processes involving DNA (e.g. replication, transcription and repair) and poses a challenge in the maintenance of genomic stability. It was shown that SPRTN participates in the binding of the AAA+ ATPase p97, well known for its function in unwinding of ubiquitinated proteins. Solving the crystal structure of the SPRTN:p97 complex and its functional characterization would allow a deeper understanding of the p97 role in DPC damage repair. Therefore, human SPRTN and p97, as well as several of their deletion mutants were overexpressed and purified by standard chromatography techniques. Subsequently, complex formation between SPRTN and p97 was tested and characterized via pull-down assays. To estimate the stoichiometry of the complex, native polyacrylamide gel electrophoresis was applied. SPRTN and p97 complex was subjected to crystallization by vapor diffusion method. Initial crystallization conditions were further optimized with the aim to obtain larger and higher quality diffracting crystals. Taken together, this set the stage for obtaining the structure of the SPRTN:p97 complex.