In this work, Fe3O4 nanoparticles (NPs) loaded inside and outside halloysite nanotubes (HNTs) were prepared and developed as the heterogeneous Fenton-like catalysts for the removal of representative organic pollutants. Characterization results indicated that the samples with Fe3O4 NPs loaded outside the HNTs lumen (Fe3O4/HNTs) and inside the HNTs lumen (Fe3O4@HNTs) were successfully prepared. Both samples had typical magnetic hysteresis loops, while Fe3O4@HNTs exhibited higher magnetization intensity. The comparative experiments showed that Fe3O4@HNTs had better Fenton-like catalytic ability than that of Fe3O4/HNTs in the degradation of various organic pollutants. Taking Rhodamine B (RhB) as an example, the adsorption thermodynamics and kinetics of RhB onto Fe3O4/HNTs and Fe3O4@HNTs were also investigated. The comparative results demonstrated that the adsorption ability of Fe3O4/HNTs was better than that of Fe3O4@HNTs. Moreover, the dissolved concentration of Fe2+ and production amount of hydroxyl radical (·OH) in the Fe3O4@HNTs-H2O2 system were significantly higher than those in the Fe3O4/HNTs-H2O2 system. Based on aforementioned comparison, the nano-confinement effect in the Fe3O4@HNTs-H2O2 system was verified. This work provides meaningful guidance for the cheap and convenient design of nanoreactors for Fenton-like applications.