The DSCPA say two individuals attempted to ship the puppies from Dublin Port to Holyhead Port in North Wales.
The dogs were held in "hugely inappropriate" conditions, cramped into small containers with "little or no space, no food or water".
The raid was part of Operation Delphin, a collaboration between animal welfare organisations and other agencies.
The puppies are thought to be about six or seven weeks old and the breeds included beagles, basset hounds, labradoodles and pomeranians.
They have now been returned to Dublin and under DSPCA care. A number of them are ill and are undergoing veterinary care at a shelter in Rathfarnham.
The operation was part of an intelligence-led raid and involved the border force intercepting two vehicles on different ferry crossings.
Ian Briggs, of the RSPCA's special operations unit, said: "These poor puppies were being carted into Wales in deeply inappropriate conditions in the early hours of the morning.
"Sadly, to unscrupulous dealers, these young pups are nothing more than a cash bonanza - and dealers would have been targeting tens of thousands of pounds from these shipments.
"This is another shocking example of people being readily prepared to act illegally and compromise the welfare of defenceless animals to make a quick buck - but, fortunately, they were stopped in their tracks."
Brian Gilles, CEO of the DSPCA, added, "We are delighted with the outcome of this operation.
"We in the DSPCA believe that cooperating with agencies on both sides of the Irish Sea in sharing intelligence, resources and cooperating together will ultimately prevail against those who are involved in this disgusting, greedy trade."

Glen Johnson said he was stepping down from Cadwgan Building Preservation Trust (CBPT) due to the harassment from a small number of unnamed people.
He said some had taken exception to the way the castle project was being run. It reopened in April.
The trust, made up of 250 people, secured revamp funds, with more than £6m from the Heritage Lottery Fund.
Volunteers raised more than £200,000 to save the 900-year-old site.
Mr Johnson said: "The main reason for my resignation is to protect my family from the virtual persecution currently being dealt out by a small number of individuals who have taken exception to the castle and its trustees because the project is not precisely as they would like it."
He will continue to work as a volunteer with the group.
CBPT chairwoman Jann Tucker said: "Glen's remarkable knowledge of the castle and the history of Cardigan has played a huge part in making the site what it is today and we are pleased that he will continue to support us in the capacity of a volunteer - a role he first took up 30 years ago."
Almost 100 puppies have been seized as part of an operation into the illegal puppy trade from Ireland to the UK.
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A trustee of a group which secured the £12m restoration of Cardigan Castle has quit due to online "persecution".