diff --git a/deps/build.jl b/deps/build.jl
index 762c8724..030b1af8 100644
--- a/deps/build.jl
+++ b/deps/build.jl
@@ -189,7 +189,7 @@ const programname = pysys(python, "executable")
 
 # Get PYTHONHOME, either from the environment or from Python
 # itself (if it is not in the environment or if we are using Conda)
-PYTHONHOME = if !haskey(ENV, "PYTHONHOME") || use_conda
+PYTHONHOME = if use_conda
     # PYTHONHOME tells python where to look for both pure python
     # and binary modules.  When it is set, it replaces both
     # `prefix` and `exec_prefix` and we thus need to set it to
@@ -200,7 +200,7 @@ PYTHONHOME = if !haskey(ENV, "PYTHONHOME") || use_conda
     exec_prefix = pysys(python, "exec_prefix")
     is_windows() ? exec_prefix : pysys(python, "prefix") * ":" * exec_prefix
 else
-    ENV["PYTHONHOME"]
+    get(ENV, "PYTHONHOME", nothing)
 end
 
 # cache the Python version as a Julia VersionNumber
@@ -238,8 +238,8 @@ writeifchanged("deps.jl", """
     const pyprogramname = "$(escape_string(programname))"
     const wpyprogramname = $(wstringconst(programname))
     const pyversion_build = $(repr(pyversion))
-    const PYTHONHOME = "$(escape_string(PYTHONHOME))"
-    const wPYTHONHOME = $(wstringconst(PYTHONHOME))
+    const PYTHONHOME = $(PYTHONHOME == nothing ? nothing : "\"" * escape_string(PYTHONHOME) * "\"")
+    const wPYTHONHOME = $(PYTHONHOME == nothing ? nothing : wstringconst(PYTHONHOME))
 
     "True if we are using the Python distribution in the Conda package."
     const conda = $use_conda
diff --git a/src/pyinit.jl b/src/pyinit.jl
index 24565803..d65b0c71 100644
--- a/src/pyinit.jl
+++ b/src/pyinit.jl
@@ -31,7 +31,7 @@ function __init__()
     already_inited = 0 != ccall((@pysym :Py_IsInitialized), Cint, ())
 
     if !already_inited
-        Py_SetPythonHome(libpy_handle, PYTHONHOME, wPYTHONHOME, pyversion)
+        PYTHONHOME != nothing && Py_SetPythonHome(libpy_handle, PYTHONHOME, wPYTHONHOME, pyversion)
         if !isempty(pyprogramname)
             if pyversion.major < 3
                 ccall((@pysym :Py_SetProgramName), Void, (Cstring,), pyprogramname)
diff --git a/src/startup.jl b/src/startup.jl
index 35c88731..733a60cb 100644
--- a/src/startup.jl
+++ b/src/startup.jl
@@ -47,7 +47,7 @@ if !symbols_present
     # Only to be used at top-level - pointer will be invalid after reload
     libpy_handle = Libdl.dlopen(libpython, Libdl.RTLD_LAZY|Libdl.RTLD_DEEPBIND|Libdl.RTLD_GLOBAL)
     # need SetPythonHome to avoid warning, #299
-    Py_SetPythonHome(libpy_handle, PYTHONHOME, wPYTHONHOME, pyversion_build)
+    PYTHONHOME != nothing && Py_SetPythonHome(libpy_handle, PYTHONHOME, wPYTHONHOME, pyversion_build)
 else
     @static if is_windows()
         pathbuf = Vector{UInt16}(1024)