Tilly, a three year old red boxer with an amputated leg, went missing from Leyland on Wednesday afternoon.
Vicki Ackerman, Tilly's owner, says the mutt had been ill, and will not have eaten for four days.
"The vet said she might have liver failure," the 41 year old said, "she has just been drinking water and being sick".
Vicki, who lives in Western Drive, Leyland, says Tilly might have been swept away by a river.
"Our garden backs onto the River Lostock. she would never normally go in if it's deep, but one minute she was there and the next she had disappeared".
Anyone who spots Tilly can call Vicki on 07368471390.
Since Wednesday Vicki has been searching the river and its banks constantly.
"We just can't find her," she said.
Tilly lost her front right leg when she was just 8 years old, after a fall broke the bones in her shoulder.