The TUC research is based on figures in the Landman Economics Family Resources Survey.
The TUC suggests that by the 2016/17 financial year families with children will collectively be £11.7 billion worse off per year due to cuts.
This is compared to out-of-work families with children, who will see their collective benefits reduced by £2.34 billion.
Working families will lose £3.41 billion through the loss of child tax credits – 10 times that of the unemployed.
TUC general secretary Frances O'Grady called the figures evidence that the government's claims that cuts are designed to encourage people into work don't stand up.
"The fact is that the bulk of the cuts hit low-paid families already in work," she said. “With nearly half the total cost of welfare changes falling on working families with children, the prime minister has already failed his own new family test, announced just this week."
A spokesperson for the Department for Work and Pensions claimed the cuts are a result of the government inheriting a benefits system "in meltdown".
"[It] trapped the families it was designed to help in cycles of worklessness and welfare dependency," the spokesperson added. "Our welfare reforms will improve the lives of some of the poorest families in our communities."