The marchers, some of whom began their trek on Wednesday from municipalities across the northeastern Spanish region, were set to reach the regional capital Barcelona later in the day.
Tensions between Madrid and Catalonia have been rising since Monday, when Spain's Supreme Court sentenced nine politicians and activists to up to 13 years each in prision, Presstv Reported.
The sentences set off the worst sustained street violence Spain has seen in decades, with clashes between protesters and police, posing a major challenge both for the Spanish government and regional pro-independence authorities.
The Spanish soccer federation (RFEF) said in a statement on that Barcelona's Oct. 26 home match against Real Madrid, one of the biggest rivalries in the sport, had been postponed due to security concerns.
Friday's marchers, ranging from families pushing prams to cyclists wheeling their bicycles, took over a highway lane and other major roads as they walked peacefully towards the Catalan capital, many sporting yellow ribbons - a sign of protest against the jailing of Catalan independence leaders.
Major roads were blocked off across Catalonia and several main streets in Barcelona were closed to traffic in anticipation of the marches, as well as picket lines that had begun springing up, while regional trains and the city's metro system were running on a reduced timetable after pro-independence unions called a strike.
Barcelona's El Prat airport, forced to cancel around 150 flights this week after it was barricaded by thousands of people, was running normally for the most part, according to Spain's Ministry of Public Works. Around 36 flights operated by Vueling were cancelled on Friday due to the strike, the low-cost Spanish airline owned by IAG said on Twitter.
Barcelona town hall said 700 garbage containers were set ablaze since protests began on Monday and estimated that the city had suffered damage totaling more than 1.5 million Euros ($1.67 million).
Thursday began with largely peaceful protests as young people draped in Catalan flags tossed balls and skipped rope. The mood shifted later in the night, with protesters setting fire to cafe chairs lining the fashionable Rambla de Catalunya street in the heart of Barcelona's tourist district.
An official from Barcelona town hall said around 10 trees were set ablaze on Thursday.
Regional police said 16 people were arrested across Catalonia on Thursday, while health officials said medical aid was provided to 42 people.
Carmaker Seat, a unit of Volkswagen AG (VOWG_p.DE), said it had halted production at its plant in Martorell, near Barcelona, from Thursday afternoon until Saturday over concerns that the marches would disrupt traffic, a company spokeswoman said.
Barcelona's wholesale market, MercaBarna, said visits to its fish sellers were down 85% on Friday, while flower stalls at the market saw 90% fewer customers.
Pro-independence leaders went ahead with a 2017 referendum on independence, despite it being deemed illegal by Spanish courts, followed by a declaration that the region was breaking away from Spain. Madrid responded to this by seizing control of the Catalan administration, and putting the ringleaders on trial.
Catalonia's former leader, Carles Puigemont, who fled to Belgium after the failed independence bid, told reporters on Friday that Belgian authorities had allowed him to remain free without bail after Spain's Supreme Court targeted him with a European arrest warrant.