Julian Assange says Catalonia now faces a "Gandhian struggle" after the Catalan parliament declared independence from Spain in a contentious vote.
On Friday the Catalan parliament in Barcelona passed a motion declaring independence, however opposition parties boycotted the vote leaving the chamber half empty.
At the same time the Spanish Senate in Madrid approved direct rule of the prosperous region.
Mr Assange, the Australian founder of WikiLeaks, has been a vocal supporter of the Catalan independence push.
"An enormous defining Gandhian struggle will now commence in Catalonia to secure their declaration of independence against the full weight of the Spanish state, from the use of force, to financial interdiction, censorship, computer hacking, intelligence, propaganda and diplomacy," he tweeted following the Catalan vote.
"Spain failed to adapt to its diminishing leverage over Catalonia by moving towards a confederation or otherwise being more attractive to Catalans," he later tweeted. "If the chain is weak the carrots must be strong. The failure to flexibly adapt is rooted in Francoist structures, ideas-and families"
On October 1 the regional government held a referendum on independence, despite Spanish courts ruling it illegal, but the ballot was marred by violent clashes with police and a low turnout of 43 per cent.
Five people were hospitalised and more than 800 people reported injuries after clashes with Spanish police, who were condemned by Mr Assange at the time.
"Dear @JunckerEU. Is this 'respect for human dignity, freedom and democracy'? Activate article 7 and suspend Spain from the European Union for its clear violation of Article 2," he tweeted, referring to Jean-Claude Juncker, president of the EU.
The outspoken 45-year-old has been holed up in the Ecuadorian embassy in London since June 2012 after seeking asylum to avoid extradition to Sweden to face a rape allegation.
Swedish prosecutors dropped investigations into the allegations in May, but Mr Assange still faces arrest by British police on a charge of skipping bail if he leaves the embassy.