Cofilin plays a fundamental role in remodeling the actin cytoskeleton by binding to actin filaments and facilitating their severing and depolymerization. Disruption of actin-cofilin interactions, particularly as a result of actin mutations, has been implicated in the initiation and progression of various cancers, including skin cancer. In this study, the binding affinity of cofilin to wild-type (WT) actin and cancer-associated mutant actins (D288N, G168N, and R63Q) was investigated using steered molecular dynamics (SMD) simulations. Structural models of the actin-cofilin complex were constructed and subjected to constant‑velocity pulling to quantify the maximum rupture force as well as interaction energy components, including van der Waals and electrostatic energies. The results of the SMD simulations indicated that the maximum separation force in the WT was approximately 4000 pN, whereas this value increased to 4200, 4400, and 4700 pN for the D288N, G168N, and R63Q, respectively. Energy analysis further revealed that these mutations produced more stable interactions compared with the WT, with the R63Q (van der Waals and electrostatic energies of −600 and −2900 kJ/mol, respectively) exhibiting the strongest stabilizing effect on the actin-cofilin interface. This behavior suggests an increased binding affinity and stability of the actin-cofilin complex in the presence of these mutations. These features may potentially serve as relatively stable controls in biochemical assays related to actin filament severing. They may also provide a foundation for the design of targeted modulators that could influence the rate of actin filament turnover through the regulation of cofilin activity. Overall, the findings of this study may offer insights into the molecular consequences of cancer associated actin mutations and suggest that these mutations may play a role in the dysregulation of the cytoskeleton during cancer progression.