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
💡 If you find your CSS mix-blend-mode not working as expected (on a white background), you need to explicitly set a background-color on the underlying element. The easiest way to do so is to apply background-color: white; on the html and body elements.
difference : this subtracts the darker of the two colors from the lightest color. exclusion : similar to difference but with lower contrast. hue : creates a color with the hue of the content combined with the saturation and luminosity of the background.
The mix-blend-mode CSS property sets how an element's content should blend with the content of the element's parent and the element's background.
In the old times, adding a transform translateZ(0px) used to solve a lot of problems.
At least in my Chrome, seems to still be the case:
.box {
  background-color:yellow; 
  overflow:hidden;
  border-radius:10px;
  transform: translateZ(0px);  /* added */
}
.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=""> 
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