Systemic　cancer　therapy　is　always　accompanied　with　toxicity　to　normal　tissue,　which　has　prompted　concerted　efforts　to　develop　precise　treatment　strategies.　Herein,　we　firstly　develop　an　approach　that　enables　spatiotemporally　controlled　formation　and　rotation　of　magnetic　nanochains　in　vivo,　allowing　for　precise　mechanotherapy　of　tumor.　The　nanochain　comprised　nanocomposites　of　pheophorbide-A　(PP)　modified　iron　oxide　nanoparticle　(IONP)　and　lanthanide-doped　down-conversion　NP　(DCNP).　In　a　permanent　magnetic　field,　the　nanocomposites　would　be　aligned　to　form　nanochain.　Next,　MnO2　NPs　were　subsequently　administered　to　accumulate　in　tumor　as　suppliers　of　Mn2+,　which　coordinates　with　PP　to　immobilize　the　nanochain.　In　a　rotating　magnetic　field,　the　nanochain　would　rapidly　rotate,　leading　to　apoptosis/necrosis　of　tumor　cell.　The　nanochain　showed　high　T2-MR　and　NIR-II　fluorescence　imaging　signals,　which　facilitated　guided　therapy.　The　strategy　has　great　potential　in　practical　applications.　©　2022　Wiley-VCH　GmbH.