A novel, rapid and environmentally friendly magnetic solid-phase extraction (MSPE) method has been developed for the enrichment of tenofovir disoproxil fumarate (TDF) before analysis by high performance liquid chromatography (HPLC). A magnetically separable NiFe₂O₄/multiwalled carbon nanotube (NiFe₂O₄/MWCNT) adsorbent showed an excellent affinity to TDF. The ionic liquid (IL) [C₈mim][PF₆] was used to substitute for toxic and environmentally hazardous solvents as a green eluent. Analytical parameters of the proposed method were investigated and a good linear range (4.0–400.0 ng mL⁻¹), limit of detection (LOD, 0.67 ng mL⁻¹), limit of quantification (LOQ, 2.2 ng mL⁻¹) and precision (RSD of 6.7%, n = 5) were obtained. This proposed method was successfully applied to the analysis of real samples with good spiked recoveries in the range of 91.4–99.6%, proving that this method was competitive in practical applications. The results indicated that the developed method would be a green method for rapid determination of TDF at trace levels in real samples.