The development of stimuliâresponsively degradable porous carriers for both controlled drug release and high biosafety is vitally important to their clinical translation, but still challenging at present. A new type of porphyrinâiron metal organic framework (FeâMOF) nanocrystals is engineered here as acidâdegradable drug carrier and hydrogen donor by the coordination between porphyrin and zeroâvalence Fe atom. FeâMOF nanocrystals exhibit excellent acidâresponsive degradation for H2 generation and simultaneous release of the loaded drug for combined hydrogenâchemotherapy of cancer multidrug resistance (MDR) and metastasis and for local hydrogen eradication of the offâtarget induced toxic side effects of the drug to normal cells/tissues. Mechanistically, released H2 assists chemotherapeutic drug to efficiently inhibit cancer metastasis by immunoactivating intratumoral M1âphenotype macrophages and consequently downregulating the expression of metastasisârelated matrix metalloproteinaseâ2 (MMPâ2) and can also downregulate the expressions of both Pâglycoprotein (Pâgp) protein and adenosine triphosphate (ATP) in MDR cancer cells to sensitize chemotherapeutic drug for enhanced damage to mitochondria and DNA. High antiâMDR/antimetastasis efficacies and high biocompatibility endow FeâMOF nanocrystals and the FeâMOFâbased nanomedicine with high potential for clinical translation.