Objective <p>Pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) increases the sensitivity of multiple myeloma (MM) cells to bortezomib by upregulating lysosome-associated membrane protein 2 (LAMP2), while their clinical role in MM patients is unclear. This study aimed to assess the intercorrelation between PHLPP and LAMP2, as well as their associations with treatment response and survival in MM patients who received induction treatment with bortezomib.</p> Methods <p>A total of 59 MM patients who received induction treatment with bortezomib were included. PHLPP and LAMP2 were detected by quantitative polymerase chain reaction in bone marrow plasma cells that were collected before treatment. Treatment response, progression-free survival (PFS), and overall survival (OS) were assessed.</p> Results <p>PHLPP was positively correlated with LAMP2, whether they were considered as continuous variables (<i>r</i> = 0.469, <i>P</i> &lt; 0.001) or categorized as high and low expressions (<i>P</i> = 0.003). PHLPP and LAMP2 were elevated in patients who achieved complete remission (CR) versus those who did not, as well as in patients who achieved partial remission (PR) and above versus those who had less than PR (all <i>P</i> &lt; 0.05). By chi-square test, high PHLPP (cut by the median) was linked with the achievement of PR and above (<i>P</i> = 0.015), and high LAMP2 (cut by the median) was related to the achievement of CR (<i>P</i> = 0.030). High PHLPP (<i>P</i> = 0.016) and LAMP2 (<i>P</i> = 0.037) were associated with prolonged PFS, but not OS (both <i>P</i> &gt; 0.05).</p> Conclusion <p>PHLPP is positively correlated with LAMP2, and their high expressions predict favorable treatment response and PFS in MM patients who receive induction treatment with bortezomib.</p>