One of his sons, Wiley Holland, removed to Madison County, Mississippi, where, in 1852, there was a severe smallpox epidemic. Wiley sent his father a message to come render help in this terrible time of sickness and death.
Before starting out on the journey to Mississippi in a horse-drawn buggy, Dr. Daniel Holland made his will in May of the same year stating:
In the name of God, Amen. I Daniel Holland, Sr., of the County of Calloway and State of Kentucky, being of sound mind and disposing memory, expecting to take a journey into a new Country of some considerable length and, calling to mind, the uncertainty of human life, and being desirous should I not be permitted to return, to dispose of all such worldly estate as it hath pleased God to bless me with.
Two months later, Daniel Holland returned home in the buggy in which he departed on the trip, but not alive. He had contracted the disease he had gone to Mississippi to treat, and died enroute home. His faithful horse brought his body safely in the buggy to his home. Thus he was buried 20 July 1852, at the age of fifty-one years, in the small family cemetery on his farm which still exists.