Quantum anomalous Hall (QAH) insulators with high Chern number host multiple dissipationless chiral edge channels, which are of fundamental interest and promising for applications in spintronics and quantum computing. Here, we propose a dynamic approach for achieving high-Chern-number QAH phases in periodically driven two-dimensional higher-order topological insulators (HOTIs) irradiated by circularly polarized light (CPL). In particular, we consider two representative kinds of HOTIs which are characterized by a quantized quadruple moment and the second Stiefel-Whitney number, respectively. Using the Floquet formalism for periodically driven systems, we demonstrate that QAH insulators with tunable Chern numbers up to four can be achieved. Moreover, we show by first-principles calculations that the monolayer graphdiyne, a realistic HOTI, is an ideal material candidate. Remarkably, the irradiation of CPL does not destroy the quantized quadruple moment in periodically driven HOTIs, leading to an exotic mixed phase harboring both high Chern numbers and higher-order topology. Our work not only establishes a strategy for designing high-Chern-number QAH insulators in periodically driven HOTIs, but also provides a powerful approach to investigate exotic topological states in nonequilibrium cases.