Javascript Regex- replace sequence of characters with same number of another character

Use a function for replacement instead:

var txt = "==Hello==";
txt = txt.replace(/(==)([^=]+)(==)/g, function ($0, $1, $2, $3) {
    return $1 + (new Array($2.length + 1).join("~")) + $3;
});

alert(txt);
//-> "==~~~~~=="