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."
Almost 100 puppies have been seized as part of an operation into the illegal puppy trade from Ireland to the UK.