The energy secretary also claimed an independent Scotland would help to deliver a strong and more resilient supply of energy with lower costs.
Mr Matheson insisted hydrogen – which can be used in fuel cells generating electricity or heat – could help Scotland meet its net zero targets.
His comments come as he will travel to Brussels this week to promote Scottish hydrogen during European Hydrogen week.
The Scottish Government say he will participate in meetings on North Sea hydrogen infrastructure with key industry figures and ministers from Belgium and the Netherlands.
The trip follows the publication of the latest paper in the Building a New Scotland series last week, which set out plans to enhance Scotland’s renewable energy production, such as hydrogen, onshore and offshore wind, tidal and wave energy and puts renewables at the centre of a new Scottish economy.
It also proposes new market frameworks to develop and deploy renewable hydrogen and Carbon Capture Storage (CCS), proposals that cannot currently be delivered as energy is a reserved matter.
However, the Scottish Government’s clean energy strategy was dealt a blow after recent research in the academic journal Joule, carried out by Jan Rosenow, Europe director at the Regulatory Assistance Project think tank in Brussels, found that hydrogen would not have a major role in the future of heating homes across the UK.
Ms Rosenow was reported last month to say: “Using hydrogen for heating may sound attractive at first glance, however, all of the independent research on this topic comes to the same conclusion: heating with hydrogen is a lot less efficient and more expensive than alternatives such as heat pumps, district heating and solar thermal.
“Rather than hoping for hydrogen to eventually be able to replace fossil gas used for heating our buildings we should focus on speeding up the roll-out of energy efficiency and heat pumps, technologies consistently identified as critical for reducing carbon emissions from buildings.”
Last year, the Scottish Government published its draft hydrogen action plan, setting out how to boost the sector, with the goal of having 5 gigawatts (GW) of installed production capacity by 2030 – rising to 25GW by 2045.
Mr Matheson said: “Hydrogen may be Scotland’s greatest industrial opportunity since oil and gas. It will play a key role in delivering net zero in industrial and heavy transport use and in the domestic economy, potentially heating our homes and buildings and there is significant export potential.
“Scotland is an energy rich country, becoming independent would give us the powers and levers to reform the energy market and ensure a stronger, more resilient supply with lower costs.”
The Scottish Liberal Democrats said the use of hydrogen needs to play an “integral part of the country’s future energy mix”, however, “does not require the break-up of the UK”.
Liam McArthur MSP, the party’s energy spokesperson said: "In fact, uncertainty around the future of the UK energy market is only likely to discourage investment and hold back development of hydrogen.
"We know that the SNP will always prioritise independence above everything else. However, the SNP’s obsession with the constitution puts at risk Scotland’s ability to fulfil our renewable potential."