  In the framework of 2HDM, we explore the wrong-sign Yukawa region with direct
and indirect searches up to one-loop level. The direct searches include the
latest $H/A \to f\bar f, VV, Vh, hh$ reports at current LHC, and the study of
indirect Higgs precision measurements works with current LHC, future HL-LHC and
CEPC. At tree level of Type-II 2HDM, for degenerate heavy Higgs mass
$m_A=m_H=m_{H^\pm}<800$ GeV, the wrong-sign Yukawa regions are excluded largely
except for the tiny allowed region around $\cos(\beta-\alpha)\in(0.2,0.3)$
under the combined constraints. The excluded region is also nearly independent
of parameter $m_{12}$ or $\lambda v^2=m_A^2-m_{12}^2/(\sin \beta \cos \beta)$.
The situation changes a lot after including loop corrections to the indirect
searches, for example $m_A=800 $ GeV, the region with $\lambda v^2<0$ will be
stronger constrained to be totally excluded. Whilst $\lambda v^2>0$ would get
larger survived wrong-sign region, such as $\cos(\beta-\alpha) \in (0,0.3)$ for
$\sqrt{\lambda v^2}=400$ GeV, under combined restrictions.
