Pakistan are touring South Africa for the first time since 2007, with the first Test beginning on February 1.
"This series is one of the biggest challenges of my captaincy tenure but I am confident that we can pose a serious threat to South Africa," Misbah told Reuters.
"The coming series is very important for Pakistan cricket because we have mostly played our cricket in South Asia or the UAE since 2010.
"South Africa has one of the best pace attacks in the world so we have to stand up and be counted. If we can post decent totals in the Tests I know our bowlers will deliver."
South Africa completed a 2-0 series victory over New Zealand in Port Elizabeth on Monday.