If you use animation effect before mix-blend-mode property you will not get mix blend mode.
Once you remove the animation class or disable animation, then mix-blend-mode will work.
What is the problem? I spent hours to solve just this simple thing. Please, help
.box {
  background-color:yellow; 
  overflow:hidden;
  border-radius:10px;
}
.box img{ mix-blend-mode:multiply}
.animate{  
  border:1px solid red;
  width:30px; height:30px;
  animation: spin 2s infinite linear;
}
@keyframes spin {
  0% {  transform: rotate(0deg); }
  100% { transform: rotate(1turn); }
}
<div class="animate">123</div>
<div class="box">
  <img src="https://placeimg.com/400/200/animals" alt=""> 
</div>
mix blend should take effect anyway