We subsequently employed the JAK2/STAT3 signaling pathway inhibitor FLLL32 in a rescue experiment within the ISG15 overexpression group to further confirm whether ISG15’s impact on the proliferation, invasion, and migration capabilities of ccRCC is mediated through the regulation of the JAK2/STAT3 signaling pathway. Here, JAK2 is linked to nonpapillary renal cell carcinoma.