The Paraguayan is currently on loan at Spanish outfit Malaga, but will be a free agent when his contract with the Premier League champions expires at the end of the season.
It had been expected that the 31-year-old would join Malaga on a permanent basis, but Robson Lima has opened up a move to Brazil.
"Talks were very good, Botafogo are a very serious club. The player is excited about the possibility. We are negotiating with Botafogo but we can't say if the deal will work out in the end," Lima told Lancenet.
Santa Cruz has scored 25 goals in 92 games for his country.