European Union has a strong commitment to dealing with the issue of nuclear proliferation. Based on European security strategy, nuclear proliferation could generate as the biggest thread in Europe. Iran appears as one of the nuclear-based energy states; in that process, Iran faces many problems and consequences. The responses and views from the surrounding states turn into worries as the nuclear-based program is suspected to be the source of Iran’s nuclear proliferation if the monitorization from IAEA is absent. To respond Iran’s nuclear proliferation, several other states and international organizations take strict actions, from diplomacy to sanction. Iran’s nuclear proliferation has invited the European Union to also deal with the issue. Effective multilateralism as the European Security Strategy Base becomes one of the key action for European Union in opposing nuclear proliferation. In dealing with Iran’s nuclear proliferation issue, European Union is able to influence and push the P5+1’s multilateral diplomacy in ensuring that Iran’s nuclear program is totally aimed for peaceful projects. Multilateralism is one of the EU’s international identity and also the principle of EU’s actions. The effort in finding diplomatic solutions for the issue of nuclear proliferation is the most ambitious and highly risked action taken by the EU to ensure the international security.