1、单窗体
private void MainForm_Closing(object sender, System.ComponentModel.CancelEventArgs e)
  {
      
    if(MessageBox.Show("是否退出本系统?","确认...",MessageBoxButtons.YesNo,MessageBoxIcon.Question)==DialogResult.Yes)
    {
     e.Cancel = false;
    }
    else
    {
     e.Cancel = true;
    }
  }

2、多窗体
private void frmMain_Closing(object sender, System.ComponentModel.CancelEventArgs e)
  {
   DialogResult result;

   result = MessageBox.Show("您确定要退出系统吗?","请确认",MessageBoxButtons.OKCancel,MessageBoxIcon.Question);
   if (result == DialogResult.OK)
   {
    foreach(Form frm in this.MdiChildren)
    {
     frm.Close();
    }
    Application.Exit();
   }
   else
    e.Cancel = true;
  }
当然可以根据需要写出不同分枝,比如提示是否保存,等等

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