Lithium, as one of the strategic and critical elements in battery manufacturing industries and clean energy technologies, holds considerable economic and strategic importance. The aim of this research is to identify areas prospective for lithium mineralization in a part of the Sanandaj–Sirjan zone (the 1:100,000 Hamadan sheet) using geochemical stream sediments data. Due to its complex tectonic history and high diversity of rocks, this region possesses suitable potential for lithium mineralization. In this research, the geochemical data were first pre-processed and then processed and interpreted using a combined approach including area-weighted averaging based on lithological units, dilution correction, Sequential Factor Analysis, the Geochemical Mapping Prospectivity Index (GMPI) and Concentration–Area fractal modeling. Comparison of the results showed that the C–A fractal method is better in accurately separating lithium geochemical anomalies from the background and identifying promising zones than the dilution correction method. The final results indicate that the most important areas with high mineralization potential are concentrated in the western and southwestern parts of the study area and show significant correspondence with pegmatite–granite and cordierite hornfels rock units. This research demonstrates that the use of the catchment basin approach and fractal models has high efficiency in the targeted exploration of lithium.