Aged between five and 13, they appeared to have drunk a bottle of pesticide, officials say. Police have not ruled out suicide.
The parents of the three girls and a boy had reportedly left the village, near Bijie city, in search of work.
The area is one of the poorest in the country and has seen previous deaths of abandoned children.
Chinese state media report that the mother of the four siblings left three years ago, followed by their father in March.
The children had reportedly dropped out of school a month ago, according to the Xinhua news agency. It added that their only food was corn and preserved meat.
The mass urban migration of Chinese parents looking for work has led to millions of children being left behind in villages; many of them are cared for by grandparents.
Correspondents say that such children can be highly vulnerable.
Three years ago there was a national outcry after five abandoned children died in Bijie.
The children had suffocated inside a rubbish bin where they were sheltering, after apparently lighting a fire to keep warm.
Chinese officials have said that at least 80 million people live below the poverty line, surviving on less than $1 (Â£0.65) a day.
Police are investigating the apparent pesticide poisoning of four abandoned siblings in rural south-west China.