diff --git a/__tests__/response/set.test.js b/__tests__/response/set.test.js
index c8a19c1ef..44b1544d9 100644
--- a/__tests__/response/set.test.js
+++ b/__tests__/response/set.test.js
@@ -43,3 +43,21 @@ describe('ctx.set(object)', () => {
     assert.strictEqual(ctx.response.header.bar, '2')
   })
 })
+
+describe('ctx.set(object) Content-Type singleton guard', () => {
+  it('should throw when Content-Type is set to an array via the object form', () => {
+    const ctx = context()
+    assert.throws(
+      () => ctx.set({ 'Content-Type': ['text/html', 'text/plain'] }),
+      { message: 'Assign multiple Content-Type for response header is not allowed' }
+    )
+  })
+
+  it('should throw regardless of header name casing in the object form', () => {
+    const ctx = context()
+    assert.throws(
+      () => ctx.set({ 'content-type': ['application/json', 'text/plain'] }),
+      { message: 'Assign multiple Content-Type for response header is not allowed' }
+    )
+  })
+})
diff --git a/lib/response.js b/lib/response.js
index 9b6741476..8534d8a3d 100644
--- a/lib/response.js
+++ b/lib/response.js
@@ -543,7 +543,12 @@ module.exports = {
       }
       this.res.setHeader(field, val)
     } else {
-      Object.keys(field).forEach(header => this.res.setHeader(header, field[header]))
+      Object.keys(field).forEach(header => {
+        if (header.toLowerCase() === 'content-type') {
+          assert(!Array.isArray(field[header]), 'Assign multiple Content-Type for response header is not allowed')
+        }
+        this.res.setHeader(header, field[header])
+      })
     }
   },